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  • Suppression from beyond the grave
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Yosuke Togashi, Hiroyoshi Nishikawa

    Suppression from beyond the grave Suppression from beyond the grave, Published online: 16 November 2017; doi:10.1038/ni.3870 NatureArticleSnippet(type=standfirst, markup= Adenosine produced by apoptotic regulatory T cells (Treg cells) has a more important immunosuppressive role in the tumor microenvironment than that of live Treg cells. This discovery raises the possibility of novel strategies for cancer immunotherapy. , isJats=true)

    更新日期:2017-11-17
  • Feeling stressed? It might be your T cells
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Laura Strauss, Nikolaos Patsoukis, Vassiliki A Boussiotis

    Feeling stressed? It might be your T cells Feeling stressed? It might be your T cells, Published online: 16 November 2017; doi:10.1038/ni.3872 NatureArticleSnippet(type=standfirst, markup= Abolishing signals mediated by the inhibitory receptor PD-1 results in a systemic decrease in tryptophan and tyrosine, which leads to a striking deficiency in the neurotransmitters serotonin and dopamine in the brain and anxiety-like behavior and exacerbated fear. , isJats=true)

    更新日期:2017-11-17
  • Trained macrophages support hygiene hypothesis
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Bérengère de Laval, Michael H Sieweke

    Trained macrophages support hygiene hypothesis Trained macrophages support hygiene hypothesis, Published online: 16 November 2017; doi:10.1038/ni.3874 NatureArticleSnippet(type=standfirst, markup= Replacement of resident alveolar macrophages by monocyte-derived macrophages after herpesvirus infection protects against asthma. , isJats=true)

    更新日期:2017-11-17
  • Inflammatory lipids
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Laurie A. Dempsey

    Inflammatory lipids Inflammatory lipids, Published online: 16 November 2017; doi:10.1038/ni.3876

    更新日期:2017-11-17
  • Interferons control fungus
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Zoltan Fehervari

    Interferons control fungus Interferons control fungus, Published online: 16 November 2017; doi:10.1038/ni.3880

    更新日期:2017-11-17
  • Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao

    Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus, Published online: 16 November 2017; doi:10.1038/ni1217-1361a

    更新日期:2017-11-17
  • Tumor control
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Ioana Visan

    Tumor control Tumor control, Published online: 16 November 2017; doi:10.1038/ni.3878

    更新日期:2017-11-17
  • Charles D. Surh 1960–2017
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Janko Nikolich-Žugich

    Charles D. Surh 1960–2017 Charles D. Surh 1960–2017, Published online: 16 November 2017; doi:10.1038/ni.3871

    更新日期:2017-11-17
  • Suppression from beyond the grave
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Yosuke Togashi, Hiroyoshi Nishikawa

    Suppression from beyond the grave Suppression from beyond the grave, Published online: 16 November 2017; doi:10.1038/ni.3870 NatureArticleSnippet(type=standfirst, markup= Adenosine produced by apoptotic regulatory T cells (Treg cells) has a more important immunosuppressive role in the tumor microenvironment than that of live Treg cells. This discovery raises the possibility of novel strategies for cancer immunotherapy. , isJats=true)

    更新日期:2017-11-17
  • Feeling stressed? It might be your T cells
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Laura Strauss, Nikolaos Patsoukis, Vassiliki A Boussiotis

    Feeling stressed? It might be your T cells Feeling stressed? It might be your T cells, Published online: 16 November 2017; doi:10.1038/ni.3872 NatureArticleSnippet(type=standfirst, markup= Abolishing signals mediated by the inhibitory receptor PD-1 results in a systemic decrease in tryptophan and tyrosine, which leads to a striking deficiency in the neurotransmitters serotonin and dopamine in the brain and anxiety-like behavior and exacerbated fear. , isJats=true)

    更新日期:2017-11-17
  • Trained macrophages support hygiene hypothesis
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Bérengère de Laval, Michael H Sieweke

    Trained macrophages support hygiene hypothesis Trained macrophages support hygiene hypothesis, Published online: 16 November 2017; doi:10.1038/ni.3874 NatureArticleSnippet(type=standfirst, markup= Replacement of resident alveolar macrophages by monocyte-derived macrophages after herpesvirus infection protects against asthma. , isJats=true)

    更新日期:2017-11-17
  • Inflammatory lipids
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Laurie A. Dempsey

    Inflammatory lipids Inflammatory lipids, Published online: 16 November 2017; doi:10.1038/ni.3876

    更新日期:2017-11-17
  • Interferons control fungus
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Zoltan Fehervari

    Interferons control fungus Interferons control fungus, Published online: 16 November 2017; doi:10.1038/ni.3880

    更新日期:2017-11-17
  • Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao

    Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus Corrigendum: The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus, Published online: 16 November 2017; doi:10.1038/ni1217-1361a

    更新日期:2017-11-17
  • Tumor control
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Ioana Visan

    Tumor control Tumor control, Published online: 16 November 2017; doi:10.1038/ni.3878

    更新日期:2017-11-17
  • Charles D. Surh 1960–2017
    Nat. Immunol. (IF 21.506) Pub Date : 2017-11-16
    Janko Nikolich-Žugich

    Charles D. Surh 1960–2017 Charles D. Surh 1960–2017, Published online: 16 November 2017; doi:10.1038/ni.3871

    更新日期:2017-11-17
  • Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-30
    Tomasz Maj, Wei Wang, Joel Crespo, Hongjuan Zhang, Weimin Wang, Shuang Wei, Lili Zhao, Linda Vatan, Irene Shao, Wojciech Szeliga, Costas Lyssiotis, J Rebecca Liu, Ilona Kryczek, Weiping Zou

    Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumorOxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor, Published online: 30 October 2017; doi:10.1038/ni.3868NatureArticleSnippet(type=short-summary, markup=The tumor microenvironment represents a stressful cellular environment. Zou and colleagues show that Treg cells in tumors have heightened sensitivity to apoptosis, but unexpectedly this increases their suppressive potency., isJats=true)

    更新日期:2017-11-10
  • Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-23
    Michio Miyajima, Baihao Zhang, Yuki Sugiura, Kazuhiro Sonomura, Matteo M Guerrini, Yumi Tsutsui, Mikako Maruya, Alexis Vogelzang, Kenji Chamoto, Kurara Honda, Takatoshi Hikida, Satomi Ito, Hongyan Qin, Rikako Sanuki, Keiichiro Suzuki, Takahisa Furukawa, Yasushi Ishihama, Fumihiko Matsuda, Makoto Suematsu, Tasuku Honjo, Sidonia Fagarasan

    Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behaviorMetabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior, Published online: 23 October 2017; doi:10.1038/ni.3867NatureArticleSnippet(type=short-summary, markup=Fagarasan and colleagues show that excessive activation of T cells in mice deficient in the inhibitory receptor PD-1 causes a systemic decrease in tryptophan and tyrosine, which leads to deficiency in serotonin and dopamine in the brain and behavioral changes., isJats=true)

    更新日期:2017-11-10
  • Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-23
    Svetlana A Fayngerts, Zhaojun Wang, Ali Zamani, Honghong Sun, Amanda E Boggs, Thomas P Porturas, Weidong Xie, Mei Lin, Terry Cathopoulis, Jason R Goldsmith, Anastassios Vourekas, Youhai H Chen

    Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2, Published online: 23 October 2017; doi:10.1038/ni.3866NatureArticleSnippet(type=short-summary, markup=The polarization of leukocytes toward chemoattractants is essential for their directed migration. Chen and colleagues show that the phosphoinositide-transfer protein TIPE2 functions as a coordinator of leukocyte polarity., isJats=true)

    更新日期:2017-11-10
  • Corrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Kalpana Manthiram, Qing Zhou, Ivona Aksentijevich, Daniel L Kastner

    Corrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammationCorrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation, Published online: 18 October 2017; doi:10.1038/ni1117-1271a

    更新日期:2017-11-10
  • Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay

    Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetesErratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes, Published online: 18 October 2017; doi:10.1038/ni1117-1271c

    更新日期:2017-11-10
  • FoxP3 partners up
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    David Bending, Masahiro Ono

    FoxP3 partners upFoxP3 partners up, Published online: 18 October 2017; doi:10.1038/ni.3852NatureArticleSnippet(type=standfirst, markup=By switching its partners, FoxP3 segregates into functional and non-functional transcriptional complexes., isJats=true)

    更新日期:2017-11-10
  • TFR cells trump autoimmune antibody responses to limit sedition
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Michelle A Linterman, Kai-Michael Toellner

    TFR cells trump autoimmune antibody responses to limit seditionT<sub>FR</sub> cells trump autoimmune antibody responses to limit sedition, Published online: 18 October 2017; doi:10.1038/ni.3856NatureArticleSnippet(type=standfirst, markup=The differentiation of follicular regulatory T cells can be limited by the cytokine IL-2, preventing the emergence of autoantibodies. This research identifies these cells as key regulators of the germinal center response., isJats=true)

    更新日期:2017-11-10
  • CD28 enhances mitochondrial function
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Laurie A. Dempsey

    CD28 enhances mitochondrial functionCD28 enhances mitochondrial function, Published online: 18 October 2017; doi:10.1038/ni.3860

    更新日期:2017-11-10
  • Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-30
    Tomasz Maj, Wei Wang, Joel Crespo, Hongjuan Zhang, Weimin Wang, Shuang Wei, Lili Zhao, Linda Vatan, Irene Shao, Wojciech Szeliga, Costas Lyssiotis, J Rebecca Liu, Ilona Kryczek, Weiping Zou

    Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumorOxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor, Published online: 30 October 2017; doi:10.1038/ni.3868NatureArticleSnippet(type=short-summary, markup=The tumor microenvironment represents a stressful cellular environment. Zou and colleagues show that Treg cells in tumors have heightened sensitivity to apoptosis, but unexpectedly this increases their suppressive potency., isJats=true)

    更新日期:2017-11-10
  • Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-23
    Michio Miyajima, Baihao Zhang, Yuki Sugiura, Kazuhiro Sonomura, Matteo M Guerrini, Yumi Tsutsui, Mikako Maruya, Alexis Vogelzang, Kenji Chamoto, Kurara Honda, Takatoshi Hikida, Satomi Ito, Hongyan Qin, Rikako Sanuki, Keiichiro Suzuki, Takahisa Furukawa, Yasushi Ishihama, Fumihiko Matsuda, Makoto Suematsu, Tasuku Honjo, Sidonia Fagarasan

    Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behaviorMetabolic shift induced by systemic activation of T cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior, Published online: 23 October 2017; doi:10.1038/ni.3867NatureArticleSnippet(type=short-summary, markup=Fagarasan and colleagues show that excessive activation of T cells in mice deficient in the inhibitory receptor PD-1 causes a systemic decrease in tryptophan and tyrosine, which leads to deficiency in serotonin and dopamine in the brain and behavioral changes., isJats=true)

    更新日期:2017-11-10
  • Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-23
    Svetlana A Fayngerts, Zhaojun Wang, Ali Zamani, Honghong Sun, Amanda E Boggs, Thomas P Porturas, Weidong Xie, Mei Lin, Terry Cathopoulis, Jason R Goldsmith, Anastassios Vourekas, Youhai H Chen

    Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2, Published online: 23 October 2017; doi:10.1038/ni.3866NatureArticleSnippet(type=short-summary, markup=The polarization of leukocytes toward chemoattractants is essential for their directed migration. Chen and colleagues show that the phosphoinositide-transfer protein TIPE2 functions as a coordinator of leukocyte polarity., isJats=true)

    更新日期:2017-11-10
  • Corrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Kalpana Manthiram, Qing Zhou, Ivona Aksentijevich, Daniel L Kastner

    Corrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammationCorrigendum: The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation, Published online: 18 October 2017; doi:10.1038/ni1117-1271a

    更新日期:2017-11-10
  • Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay

    Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetesErratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes, Published online: 18 October 2017; doi:10.1038/ni1117-1271c

    更新日期:2017-11-10
  • FoxP3 partners up
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    David Bending, Masahiro Ono

    FoxP3 partners upFoxP3 partners up, Published online: 18 October 2017; doi:10.1038/ni.3852NatureArticleSnippet(type=standfirst, markup=By switching its partners, FoxP3 segregates into functional and non-functional transcriptional complexes., isJats=true)

    更新日期:2017-11-10
  • TFR cells trump autoimmune antibody responses to limit sedition
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Michelle A Linterman, Kai-Michael Toellner

    TFR cells trump autoimmune antibody responses to limit seditionT<sub>FR</sub> cells trump autoimmune antibody responses to limit sedition, Published online: 18 October 2017; doi:10.1038/ni.3856NatureArticleSnippet(type=standfirst, markup=The differentiation of follicular regulatory T cells can be limited by the cytokine IL-2, preventing the emergence of autoantibodies. This research identifies these cells as key regulators of the germinal center response., isJats=true)

    更新日期:2017-11-10
  • CD28 enhances mitochondrial function
    Nat. Immunol. (IF 21.506) Pub Date : 2017-10-18
    Laurie A. Dempsey

    CD28 enhances mitochondrial functionCD28 enhances mitochondrial function, Published online: 18 October 2017; doi:10.1038/ni.3860

    更新日期:2017-11-10
  • Germline bias dictates cross-serotype reactivity in a common dengue-virus-specific CD8+ T cell response
    Nat. Immunol. (IF 21.506) Pub Date : 
    Abigail Culshaw, Kristin Ladell, Stephanie Gras, James E McLaren, Kelly L Miners, Carine Farenc, Heleen van den Heuvel, Emma Gostick, Wanwisa Dejnirattisai, Apirath Wangteeraprasert, Thaneeya Duangchinda, Pojchong Chotiyarnwong, Wannee Limpitikul, Sirijitt Vasanawathana, Prida Malasit, Tao Dong, Jamie Rossjohn, Juthathip Mongkolsapaya, David A Price, Gavin R Screaton

    Adaptive immune responses protect against infection with dengue virus (DENV), yet cross-reactivity with distinct serotypes can precipitate life-threatening clinical disease. We found that clonotypes expressing the T cell antigen receptor (TCR) β-chain variable region 11 (TRBV11-2) were 'preferentially' activated and mobilized within immunodominant human-leukocyte-antigen-(HLA)-A*11:01-restricted CD8+ T cell populations specific for variants of the nonstructural protein epitope NS3133 that characterize the serotypes DENV1, DENV3 and DENV4. In contrast, the NS3133-DENV2-specific repertoire was largely devoid of such TCRs. Structural analysis of a representative TRBV11-2+ TCR demonstrated that cross-serotype reactivity was governed by unique interplay between the variable antigenic determinant and germline-encoded residues in the second β-chain complementarity-determining region (CDR2β). Extensive mutagenesis studies of three distinct TRBV11-2+ TCRs further confirmed that antigen recognition was dependent on key contacts between the serotype-defined peptide and discrete residues in the CDR2β loop. Collectively, these data reveal an innate-like mode of epitope recognition with potential implications for the outcome of sequential exposure to heterologous DENVs.

    更新日期:2017-09-28
  • Identification of lineage-specifying cytokines that signal all CD8+-cytotoxic-lineage-fate 'decisions' in the thymus
    Nat. Immunol. (IF 21.506) Pub Date : 
    Ruth Etzensperger, Tejas Kadakia, Xuguang Tai, Amala Alag, Terry I Guinter, Takeshi Egawa, Batu Erman, Alfred Singer

    T cell antigen receptor (TCR) signaling in the thymus initiates positive selection, but the CD8+-lineage fate is thought to be induced by cytokines after TCR signaling has ceased, although this remains controversial and unproven. We have identified four cytokines (IL-6, IFN-γ, TSLP and TGF-β) that did not signal via the common γ-chain (γc) receptor but that, like IL-7 and IL-15, induced expression of the lineage-specifying transcription factor Runx3d and signaled the generation of CD8+ T cells. Elimination of in vivo signaling by all six of these 'lineage-specifying cytokines' during positive selection eliminated Runx3d expression and completely abolished the generation of CD8+ single-positive thymocytes. Thus, this study proves that signaling during positive selection by lineage-specifying cytokines is responsible for all CD8+-lineage-fate 'decisions' in the thymus.

    更新日期:2017-09-28
  • Human antibodies to the dengue virus E-dimer epitope have therapeutic activity against Zika virus infection
    Nat. Immunol. (IF 21.506) Pub Date : 
    Estefania Fernandez, Wanwisa Dejnirattisai, Bin Cao, Suzanne M Scheaffer, Piyada Supasa, Wiyada Wongwiwat, Prabagaran Esakky, Andrea Drury, Juthathip Mongkolsapaya, Kelle H Moley, Indira U Mysorekar, Gavin R Screaton, Michael S Diamond

    The Zika virus (ZIKV) epidemic has resulted in congenital abnormalities in fetuses and neonates. Although some cross-reactive dengue virus (DENV)-specific antibodies can enhance ZIKV infection in mice, those recognizing the DENV E-dimer epitope (EDE) can neutralize ZIKV infection in cell culture. We evaluated the therapeutic activity of human monoclonal antibodies to DENV EDE for their ability to control ZIKV infection in the brains, testes, placentas, and fetuses of mice. A single dose of the EDE1-B10 antibody given 3 d after ZIKV infection protected against lethality, reduced ZIKV levels in brains and testes, and preserved sperm counts. In pregnant mice, wild-type or engineered LALA variants of EDE1-B10, which cannot engage Fcg receptors, diminished ZIKV burden in maternal and fetal tissues, and protected against fetal demise. Because neutralizing antibodies to EDE have therapeutic potential against ZIKV, in addition to their established inhibitory effects against DENV, it may be possible to develop therapies that control disease caused by both viruses.

    更新日期:2017-09-28
  • Corrigendum: NF-κB control of T cell development
    Nat. Immunol. (IF 21.506) Pub Date : 
    Steve Gerondakis, Thomas S Fulford, Nicole L Messina, Raelene J Grumont

    Corrigendum: NF-κB control of T cell development Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni1017-1173a

    更新日期:2017-09-21
  • Corrigendum: IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions
    Nat. Immunol. (IF 21.506) Pub Date : 
    Chang-Han Lee, Gabrielle Romain, Wupeng Yan, Makiko Watanabe, Wissam Charab, Biliana Todorova, Jiwon Lee, Kendra Triplett, Moses Donkor, Oana I Lungu, Anja Lux, Nicholas Marshall, Margaret A Lindorfer, Odile Richard-Le Goff, Bianca Balbino, Tae Hyun Kang, Hidetaka Tanno, George Delidakis, Corrine Alford, Ronald P Taylor, Falk Nimmerjahn, Navin Varadarajan, Pierre Bruhns, Yan Jessie Zhang, George Georgiou

    Corrigendum: IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni1017-1173c

    更新日期:2017-09-21
  • Erratum: Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors
    Nat. Immunol. (IF 21.506) Pub Date : 
    Jaeyop Lee, Yu Jerry Zhou, Wenji Ma, Wanwei Zhang, Arafat Aljoufi, Thomas Luh, Kimberly Lucero, Deguang Liang, Matthew Thomsen, Govind Bhagat, Yufeng Shen, Kang Liu

    Erratum: Lineage specification of human dendritic cells is marked by IRF8 expression in hematopoietic stem cells and multipotent progenitors Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni1017-1173e

    更新日期:2017-09-21
  • IFN-λ 'guts' neutrophil-mediated inflammation
    Nat. Immunol. (IF 21.506) Pub Date : 
    Emily A Hemann, Johannes Schwerk, Ram Savan

    IFN-λ 'guts' neutrophil-mediated inflammation Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni.3834 Interferon-λ (IFN-λ) curbs neutrophil-mediated intestinal inflammation by diminishing the production of reactive oxygen species and subsequent oxidative stress. This regulatory process is unique to IFN-λ and is independent of interferon-induced transcription and translation programs.

    更新日期:2017-09-21
  • B cell autoimmunity at the extremes
    Nat. Immunol. (IF 21.506) Pub Date : 
    Julie Zikherman, Clifford A Lowell

    B cell autoimmunity at the extremes Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni.3840 Caveolin-1 has a critical role in orchestrating the membrane organization of B cells. In its absence, signaling via the B cell antigen receptor and B cell tolerance are impaired, which results in autoimmunity.

    更新日期:2017-09-21
  • Distinct Zika responses
    Nat. Immunol. (IF 21.506) Pub Date : 
    Laurie A. Dempsey

    Distinct Zika responses Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni.3842

    更新日期:2017-09-21
  • CMTM6 controls PD-L1
    Nat. Immunol. (IF 21.506) Pub Date : 
    Ioana Visan

    CMTM6 controls PD-L1 Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni.3844

    更新日期:2017-09-21
  • Testicular macrophage origin
    Nat. Immunol. (IF 21.506) Pub Date : 
    Zoltan Fehervari

    Testicular macrophage origin Nature Immunology, Published online: 19 September 2017; doi:10.1038/ni.3846

    更新日期:2017-09-21
  • IFN-λ 'guts' neutrophil-mediated inflammation
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Emily A Hemann, Johannes Schwerk, Ram Savan

    Interferon-λ (IFN-λ) curbs neutrophil-mediated intestinal inflammation by diminishing the production of reactive oxygen species and subsequent oxidative stress. This regulatory process is unique to IFN-λ and is independent of interferon-induced transcription and translation programs.

    更新日期:2017-09-19
  • Disentangling the manifold functions of RORγt
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Thomas Korn

    A two-amino-acid substitution in the transcription factor RORγt disrupts its effect in establishing the transcriptional program of TH17 cells while leaving its function in the development of thymocytes and lymphoid-tissue–inducer cells largely intact.

    更新日期:2017-09-19
  • B cell autoimmunity at the extremes
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Julie Zikherman, Clifford A Lowell

    Caveolin-1 has a critical role in orchestrating the membrane organization of B cells. In its absence, signaling via the B cell antigen receptor and B cell tolerance are impaired, which results in autoimmunity.

    更新日期:2017-09-19
  • (T)Betting on innate lymphoid cells in CNS inflammatory disease
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Melissa A Brown, Abigail E Russi

    T-bet+NKp46+ subsets of group 1 and group 3 innate lymphoid cells within the meninges initiate neuroinflammation in central nervous system (CNS)-demyelinating disease by regulating both the stability of pathogenic T-bet+ T cells and their access to the CNS.

    更新日期:2017-09-19
  • Ontogeny and function of murine epidermal Langerhans cells
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Daniel H Kaplan

    Langerhans cells (LCs) are epidermis-resident antigen-presenting cells that share a common ontogeny with macrophages but function as dendritic cells (DCs). Their development, recruitment and retention in the epidermis is orchestrated by interactions with keratinocytes through multiple mechanisms. LC and dermal DC subsets often show functional redundancy, but LCs are required for specific types of adaptive immune responses when antigen is concentrated in the epidermis. This Review will focus on those developmental and functional properties that are unique to LCs.

    更新日期:2017-09-19
  • IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-28
    Achille Broggi, Yunhao Tan, Francesca Granucci, Ivan Zanoni

    Interferon-λ (IFN-λ) is a central regulator of mucosal immunity; however, its signaling specificity relative to that of type I interferons is poorly defined. IFN-λ can induce antiviral interferon-stimulated genes (ISGs) in epithelia, while the effect of IFN-λ in non-epithelial cells remains unclear. Here we report that neutrophils responded to IFN-λ. We found that in addition to inducing ISG transcription, IFN-λ (but not IFN-β) specifically activated a translation-independent signaling pathway that diminished the production of reactive oxygen species and degranulation in neutrophils. In mice, IFN-λ was elicited by enteric viruses and acted on neutrophils to decrease oxidative stress and intestinal damage. Thus, IFN-λ acted as a unique immunomodulatory agent by modifying transcriptional and non-translational neutrophil responses, which might permit a controlled development of the inflammatory process.

    更新日期:2017-09-19
  • The immunology of the allergy epidemic and the hygiene hypothesis
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-19
    Bart N Lambrecht, Hamida Hammad

    Lambrecht and Hammad discuss how microbial diversity or dysbiosis influences epithelial barrier tissues and the impact of such interactions on the development of allergic disease.

    更新日期:2017-09-19
  • The RNA helicase DDX46 inhibits innate immunity by entrapping m6A-demethylated antiviral transcripts in the nucleus
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-28
    Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao

    DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element. After viral infection, DDX46 recruited ALKBH5, an 'eraser' of the RNA modification N6-methyladenosine (m6A), via DDX46's DEAD helicase domain to demethylate those m6A-modified antiviral transcripts. It consequently enforced their retention in the nucleus and therefore prevented their translation and inhibited interferon production. DDX46 also suppressed antiviral innate immunity in vivo. Thus, DDX46 inhibits antiviral innate responses by entrapping selected antiviral transcripts in the nucleus by erasing their m6A modification, a modification normally required for export from the nucleus and translation.

    更新日期:2017-09-19
  • Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-21
    Sung Ho Park, Kyuho Kang, Eugenia Giannopoulou, Yu Qiao, Keunsoo Kang, Geonho Kim, Kyung-Hyun Park-Min, Lionel B Ivashkiv

    Cross-regulation of Toll-like receptor (TLR) responses by cytokines is essential for effective host defense, avoidance of toxicity and homeostasis, but the underlying mechanisms are not well understood. Our comprehensive epigenomics approach to the analysis of human macrophages showed that the proinflammatory cytokines TNF and type I interferons induced transcriptional cascades that altered chromatin states to broadly reprogram responses induced by TLR4. TNF tolerized genes encoding inflammatory molecules to prevent toxicity while preserving the induction of genes encoding antiviral and metabolic molecules. Type I interferons potentiated the inflammatory function of TNF by priming chromatin to prevent the silencing of target genes of the transcription factor NF-κB that encode inflammatory molecules. The priming of chromatin enabled robust transcriptional responses to weak upstream signals. Similar chromatin regulation occurred in human diseases. Our findings reveal that signaling crosstalk between interferons and TNF is integrated at the level of chromatin to reprogram inflammatory responses, and identify previously unknown functions and mechanisms of action of these cytokines.

    更新日期:2017-09-19
  • T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-14
    Brandon Kwong, Rejane Rua, Yuanyuan Gao, John Flickinger, Yan Wang, Michael J Kruhlak, Jinfang Zhu, Eric Vivier, Dorian B McGavern, Vanja Lazarevic

    The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46+ innate lymphoid cells (ILCs) in the initiation of CD4+ TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46+ ILCs profoundly impaired the ability of myelin-reactive TH17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity. T-bet-dependent NKp46+ ILCs localized in the meninges and acted as chief coordinators of meningeal inflammation by inducing the expression of proinflammatory cytokines, chemokines and matrix metalloproteinases, which together facilitated T cell entry into CNS parenchyma. Our findings uncover a detrimental role of T-bet-dependent NKp46+ ILCs in the development of CNS autoimmune disease.

    更新日期:2017-09-19
  • A two-amino-acid substitution in the transcription factor RORγt disrupts its function in TH17 differentiation but not in thymocyte development
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-28
    Zhiheng He, Jian Ma, Ruiqing Wang, Jing Zhang, Zhaofeng Huang, Fei Wang, Subha Sen, Ellen V Rothenberg, Zuoming Sun

    The transcription factor RORγt regulates differentiation of the TH17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents TH17 cell–mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγtM) that 'preferentially' disrupted TH17 differentiation but not thymocyte development. Mice expressing RORγtM were resistant to EAE associated with defective TH17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγtM showed less ubiquitination at Lys69 that was selectively required for TH17 differentiation but not T cell development. This study will inform the development of treatments that selectively target TH17 cell–mediated autoimmunity but do not affect thymocyte development or induce lymphoma.

    更新日期:2017-09-19
  • Asynchronous lineage priming determines commitment to T cell and B cell lineages in fetal liver
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-21
    Claire Berthault, Cyrille Ramond, Odile Burlen-Defranoux, Guillaume Soubigou, Sylvestre Chea, Rachel Golub, Pablo Pereira, Paulo Vieira, Ana Cumano

    The molecular events that initiate lymphoid-lineage specification remain unidentified because the stages of differentiation during which lineage commitment occurs are difficult to characterize. We isolated fetal liver progenitor cells undergoing restriction of their differentiation potential toward the T cell–innate lymphoid cell lineage or the B cell lineage. Transcripts that defined the molecular signatures of these two subsets were sequentially upregulated in lympho-myeloid precursor cells and in common lymphoid progenitor cells, respectively, and this preceded lineage restriction; this indicates that T cell–versus–B cell commitment is not a binary fate 'decision'. The T cell–bias and B cell–bias transcriptional programs were frequently co-expressed in common lymphoid progenitor cells and were segregated in subsets biased toward T cell differentiation or B cell differentiation, after interleukin 7 (IL-7) signaling that controlled the number of progenitor cells engaging in T cell differentiation versus B cell differentiation.

    更新日期:2017-09-19
  • Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-14
    Susana Minguet, Kathrin Kläsener, Anna-Maria Schaffer, Gina J Fiala, Teresa Osteso-Ibánez, Katrin Raute, Inmaculada Navarro-Lérida, Frederike A Hartl, Maximilian Seidl, Michael Reth, Miguel A Del Pozo

    Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo. In immature Cav1-deficient B cells, altered nanoscale organization of IgM-BCRs resulted in a failure of receptor editing and a skewed repertoire of B cells expressing immunoglobulin-μ heavy chains with hallmarks of poly- and auto-reactivity, which ultimately led to autoimmunity in mice. Thus, Cav1 emerges as a cell-intrinsic regulator that prevents B cell–induced autoimmunity by means of its role in plasma-membrane organization.

    更新日期:2017-09-19
  • Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues
    Nat. Immunol. (IF 21.506) Pub Date : 2017-08-07
    Michael Delacher, Charles D Imbusch, Dieter Weichenhan, Achim Breiling, Agnes Hotz-Wagenblatt, Ulrike Träger, Ann-Cathrin Hofer, Danny Kägebein, Qi Wang, Felix Frauhammer, Jan-Philipp Mallm, Katharina Bauer, Carl Herrmann, Philipp A Lang, Benedikt Brors, Christoph Plass, Markus Feuerer

    Regulatory T cells (Treg cells) perform two distinct functions: they maintain self-tolerance, and they support organ homeostasis by differentiating into specialized tissue Treg cells. We found that epigenetic modifications defined the molecular characteristics of tissue Treg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue Treg cell populations and lymphoid T cells. Similarities in the epigenetic landscape led to the identification of a common tissue Treg cell population that was present in many organs and was characterized by gain and loss of DNA methylation that included many gene sites associated with the TH2 subset of helper T cells, such as the gene encoding cytokine IL-33 receptor ST2, as well as the production of tissue-regenerative factors. Furthermore, the ST2-expressing population was dependent on the transcriptional regulator BATF and could be expanded by IL-33. Thus, tissue Treg cells integrate multiple waves of epigenetic reprogramming that define their tissue-restricted specialization.

    更新日期:2017-09-19
  • Srebp-controlled glucose metabolism is essential for NK cell functional responses
    Nat. Immunol. (IF 21.506) Pub Date : 2017-09-18
    Nadine Assmann, Katie L O'Brien, Raymond P Donnelly, Lydia Dyck, Vanessa Zaiatz-Bittencourt, Róisín M Loftus, Paul Heinrich, Peter J Oefner, Lydia Lynch, Clair M Gardiner, Katja Dettmer, David K Finlay

    Activated natural killer (NK) cells engage in a robust metabolic response that is required for normal effector function. Using genetic, pharmacological and metabolic analyses, we demonstrated an essential role for Srebp transcription factors in cytokine-induced metabolic reprogramming of NK cells that was independent of their conventional role in the control of lipid synthesis. Srebp was required for elevated glycolysis and oxidative phosphorylation and promoted a distinct metabolic pathway configuration in which glucose was metabolized to cytosolic citrate via the citrate–malate shuttle. Preventing the activation of Srebp or direct inhibition of the citrate–malate shuttle inhibited production of interferon-γ and NK cell cytotoxicity. Thus, Srebp controls glucose metabolism in NK cells, and this Srebp-dependent regulation is critical for NK cell effector function.

    更新日期:2017-09-18
  • Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection
    Nat. Immunol. (IF 21.506) Pub Date : 
    Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato

    Interleukin 2 (IL-2) promotes Foxp3+ regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional Treg cells, IL-2 inhibits TFR cell responses.

    更新日期:2017-09-12
  • De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors
    Nat. Immunol. (IF 21.506) Pub Date : 
    Anna Johansson-Percival, Bo He, Zhi-Jie Li, Alva Kjellén, Karen Russell, Ji Li, Irma Larma, Ruth Ganss

    The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

    更新日期:2017-09-12
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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