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Overcoming the LAG3 phase problem Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 Jan Petersen, Jamie Rossjohn
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LAG3 ectodomain structure reveals functional interfaces for ligand and antibody recognition Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 Qianqian Ming, Daiana P. Celias, Chao Wu, Aidan R. Cole, Srishti Singh, Charlotte Mason, Shen Dong, Timothy H. Tran, Gaya K. Amarasinghe, Brian Ruffell, Vincent C. Luca
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Single-cell transcriptomic analysis identifies an immune-prone population in erythroid precursors during human ontogenesis Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 Changlu Xu, Jian He, Hongtao Wang, Yingnan Zhang, Jing Wu, Lu Zhao, Yue Li, Jie Gao, Guangfeng Geng, Bingrui Wang, Xiaoyuan Chen, Zhaofeng Zheng, Biao Shen, Yang Zeng, Zhijie Bai, Hua Yang, Shujuan Shi, Fang Dong, Shihui Ma, Erlie Jiang, Tao Cheng, Yu Lan, Jiaxi Zhou, Bing Liu, Lihong Shi
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Tissue-resident memory CD8+ T cells possess unique transcriptional, epigenetic and functional adaptations to different tissue environments Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 John T. Crowl, Maximilian Heeg, Amir Ferry, J. Justin Milner, Kyla D. Omilusik, Clara Toma, Zhaoren He, John T. Chang, Ananda W. Goldrath
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The humoral response and antibodies against SARS-CoV-2 infection Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 Hai Qi, Bo Liu, Xinquan Wang, Linqi Zhang
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Clonal structure, stability and dynamics of human memory B cells and circulating plasmablasts Nat. Immunol. (IF 25.606) Pub Date : 2022-06-27 Ganesh E. Phad, Dora Pinto, Mathilde Foglierini, Murodzhon Akhmedov, Riccardo L. Rossi, Emilia Malvicini, Antonino Cassotta, Chiara Silacci Fregni, Ludovica Bruno, Federica Sallusto, Antonio Lanzavecchia
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Glucocorticoids initiate regulatory T cell and stem-cell crosstalk to grow new hair Nat. Immunol. (IF 25.606) Pub Date : 2022-06-24
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TCF-1 mediates chromatin intermingling during T cell development Nat. Immunol. (IF 25.606) Pub Date : 2022-06-24
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Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche Nat. Immunol. (IF 25.606) Pub Date : 2022-06-23 Zhi Liu, Xianting Hu, Yuqiong Liang, Jingting Yu, Huabin Li, Maxim N. Shokhirev, Ye Zheng
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Using social media to promote science Nat. Immunol. (IF 25.606) Pub Date : 2022-06-20 Akiko Iwasaki
Social media has transformed the way we communicate science. Here is a step-by-step guide to promote the science of your own study or of others as a thread on Twitter.
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Deciphering immunoregulatory vulnerabilities in human cancers Nat. Immunol. (IF 25.606) Pub Date : 2022-06-20 Felipe Gálvez-Cancino, Alvaro Lladser, Sergio A. Quezada
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TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors Nat. Immunol. (IF 25.606) Pub Date : 2022-06-20 Wenliang Wang, Aditi Chandra, Naomi Goldman, Sora Yoon, Emily K. Ferrari, Son. C. Nguyen, Eric F. Joyce, Golnaz Vahedi
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When inflammation turns sour on T cells Nat. Immunol. (IF 25.606) Pub Date : 2022-06-13 Carsten A. Wagner, Pedro H. Imenez Silva
Inflamed tissue has a special milieu, with hypoxia, high levels of metabolites from anaerobic glycolysis, and acidosis. Stimulation of a proton-activated receptor, TDAG8 (GPR65), in T cells has an important role in inflammatory bowel disease by balancing pro- and anti-inflammatory signals.
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pH sensing controls tissue inflammation by modulating cellular metabolism and endo-lysosomal function of immune cells Nat. Immunol. (IF 25.606) Pub Date : 2022-06-06 Xiangjun Chen, Alok Jaiswal, Zachary Costliow, Paula Herbst, Elizabeth A. Creasey, Noriko Oshiro-Rapley, Mark J. Daly, Kimberly L. Carey, Daniel B. Graham, Ramnik J. Xavier
Extracellular acidification occurs in inflamed tissue and the tumor microenvironment; however, a systematic study on how pH sensing contributes to tissue homeostasis is lacking. In the present study, we examine cell type-specific roles of the pH sensor G protein-coupled receptor 65 (GPR65) and its inflammatory disease-associated Ile231Leu-coding variant in inflammation control. GPR65 Ile231Leu knock-in
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Systemic hypoxia drives inflammation persistence via suppression of monocytes Nat. Immunol. (IF 25.606) Pub Date : 2022-06-02
This study shows that systemic hypoxia alters the response of the bone marrow to inflammation by reducing type I interferon signaling and suppressing the accumulation of monocyte-derived macrophages in the lung. These events, in turn, hinder the resolution of lung inflammation.
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Catching the breadth of broadly protective antibodies to SARS-CoV-2 Nat. Immunol. (IF 25.606) Pub Date : 2022-06-02 Kevin R. McCarthy
Broadly protective antibodies to SARS-CoV-2 inform vaccine improvements and are directly used for treatment and prevention. New technologies are enabling the recovery of thousands of antibody examples, and workflows to rapidly identify the most potent examples are accelerating discovery.
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Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses Nat. Immunol. (IF 25.606) Pub Date : 2022-06-02 Wan-ting He, Rami Musharrafieh, Ge Song, Katharina Dueker, Longping V. Tse, David R. Martinez, Alexandra Schäfer, Sean Callaghan, Peter Yong, Nathan Beutler, Jonathan L. Torres, Reid M. Volk, Panpan Zhou, Meng Yuan, Hejun Liu, Fabio Anzanello, Tazio Capozzola, Mara Parren, Elijah Garcia, Stephen A. Rawlings, Davey M. Smith, Ian A. Wilson, Yana Safonova, Andrew B. Ward, Thomas F. Rogers, Ralph S. Baric
The emergence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed. Here, we utilized a targeted donor selection strategy to isolate
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Type 2 cytokines in the thymus activate Sirpα+ dendritic cells to promote clonal deletion Nat. Immunol. (IF 25.606) Pub Date : 2022-05-30 Elise R. Breed, Matouš Vobořil, Katherine M. Ashby, Ryan J. Martinez, Lily Qian, Haiguang Wang, Oscar C. Salgado, Christine H. O’Connor, Kristin A. Hogquist
The thymus contains a diversity of dendritic cells (DCs) that exist in defined locations and have different antigen-processing and -presenting features. This suggests that they play nonredundant roles in mediating thymocyte selection. In an effort to eliminate SIRPα+ classic DC2 subsets, we discovered that a substantial proportion expresses the surface lectin, CD301b, in the thymus. These cells resemble
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Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Emily R. Kansler, Saïda Dadi, Chirag Krishna, Briana G. Nixon, Efstathios G. Stamatiades, Ming Liu, Fengshen Kuo, Jing Zhang, Xian Zhang, Kristelle Capistrano, Kyle A. Blum, Kate Weiss, Ross M. Kedl, Guangwei Cui, Koichi Ikuta, Timothy A. Chan, Christina S. Leslie, A. Ari Hakimi, Ming O. Li
Malignancy can be suppressed by the immune system. However, the classes of immunosurveillance responses and their mode of tumor sensing remain incompletely understood. Here, we show that although clear cell renal cell carcinoma (ccRCC) was infiltrated by exhaustion-phenotype CD8+ T cells that negatively correlated with patient prognosis, chromophobe RCC (chRCC) had abundant infiltration of granzyme
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A breath of fresh macrophages ameliorates inflammation in the hypoxic lung Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Federico F. De Ponti, Charlotte L. Scott
Hypoxia alters populations of monocytes and macrophages during acute respiratory distress syndrome leading to persistent inflammation, a process that can be reversed by therapeutic administration of CSF1.
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Mapping the tumor-infiltrating immune cells during glioblastoma progression Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Senthilnath Lakshmanachetty, Siddhartha S. Mitra
The dynamic changes in immune cell infiltration that accompany glioblastoma (GBM) progression remain obscure. Single-cell RNA sequencing and flow cytometry are now used to deconstruct the tumor immune microenvironment of early- and late-stage GBMs.
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Defining an exhaustion-like program that restrains autoreactive CD8+ T cells Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27
Intra-islet CD8+ T cells from a mouse model of type 1 diabetes exhibit an exhausted phenotype that differs from the canonical T cell exhaustion observed in cancer and chronic viral infection. Deletion of the inhibitory receptor LAG3 in these cells accelerated diabetes incidence and partially reversed this restrained phenotype.
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‘Stem-like’ precursors are the fount to sustain persistent CD8+ T cell responses Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Dietmar Zehn, Robert Thimme, Enrico Lugli, Gustavo Pereira de Almeida, Annette Oxenius
Virus-specific CD8+ T cells that differentiate in the context of resolved versus persisting infections exhibit divergent phenotypic and functional characteristics, which suggests that their differentiation trajectories are governed by distinct cellular dynamics, developmental pathways and molecular mechanisms. For acute infection, it is long known that antigen-specific T cell populations contain terminally
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Epigenetic regulation of T cell exhaustion Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Julia A. Belk, Bence Daniel, Ansuman T. Satpathy
Chronic antigen stimulation during viral infections and cancer can lead to T cell exhaustion, which is characterized by reduced effector function and proliferation, and the expression of inhibitory immune checkpoint receptors. Recent studies have demonstrated that T cell exhaustion results in wholescale epigenetic remodeling that confers phenotypic stability to these cells and prevents T cell reinvigoration
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Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Alan T. Yeo, Shruti Rawal, Bethany Delcuze, Anthos Christofides, Agata Atayde, Laura Strauss, Leonora Balaj, Vaughn A. Rogers, Erik J. Uhlmann, Hemant Varma, Bob S. Carter, Vassiliki A. Boussiotis, Al Charest
Glioblastoma (GBM) is an incurable primary malignant brain cancer hallmarked with a substantial protumorigenic immune component. Knowledge of the GBM immune microenvironment during tumor evolution and standard of care treatments is limited. Using single-cell transcriptomics and flow cytometry, we unveiled large-scale comprehensive longitudinal changes in immune cell composition throughout tumor progression
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NLRP3 licenses NLRP11 for inflammasome activation in human macrophages Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Anu Gangopadhyay, Savita Devi, Shivendra Tenguria, Jessica Carriere, Huyen Nguyen, Elisabeth Jäger, Hemisha Khatri, Lan H. Chu, Rojo A. Ratsimandresy, Andrea Dorfleutner, Christian Stehlik
Intracellular sensing of stress and danger signals initiates inflammatory innate immune responses by triggering inflammasome assembly, caspase-1 activation and pyroptotic cell death as well as the release of interleukin 1β (IL-1β), IL-18 and danger signals. NLRP3 broadly senses infectious patterns and sterile danger signals, resulting in the tightly coordinated and regulated assembly of the NLRP3 inflammasome
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Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Ananda S. Mirchandani, Stephen J. Jenkins, Calum C. Bain, Manuel A. Sanchez-Garcia, Hannah Lawson, Patricia Coelho, Fiona Murphy, David M. Griffith, Ailiang Zhang, Tyler Morrison, Tony Ly, Simone Arienti, Pranvera Sadiku, Emily R. Watts, Rebecca. S. Dickinson, Leila Reyes, George Cooper, Sarah Clark, David Lewis, Van Kelly, Christos Spanos, Kathryn M. Musgrave, Liam Delaney, Isla Harper, Jonathan Scott
Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse
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Viral protein activates the NLRP1 inflammasome Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Ella Hartenian, Petr Broz
Inflammasomes function as immune-signaling platforms that assemble following pathogen detection. Direct binding of a viral protein to NLRP1 and the disruption of a previously unknown autoinhibitory NRLP1 complex drive the activation of the NLRP1 inflammasome independently of the proteasome.
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CNS Treg cells have alternative functions but run on conventional fuel Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Thomas Korn
Ectopic expression of IL-2 in the central nervous system (CNS) is sufficient to create an organ-restricted niche for tissue-resident regulatory T cells that support re-establishment of homeostasis after multiple types of tissue injury in the CNS.
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Gene delivery of interleukin 2 treats neuro-inflammation in traumatic brain injury Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26
Using a gene-delivery system, we show that ectopic expression of interleukin 2 (IL-2) within reactive astrocytes stimulates brain-specific expansion of resident regulatory T cells. Such gene delivery protects against neuroinflammation in several mouse models of disease and injury, with potential implications for patients with traumatic brain injuries.
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Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Lidia Yshii, Emanuela Pasciuto, Pascal Bielefeld, Loriana Mascali, Pierre Lemaitre, Marika Marino, James Dooley, Lubna Kouser, Stijn Verschoren, Vasiliki Lagou, Hannelore Kemps, Pascal Gervois, Antina de Boer, Oliver T. Burton, Jérôme Wahis, Jens Verhaert, Samar H. K. Tareen, Carlos P. Roca, Kailash Singh, Carly E. Whyte, Axelle Kerstens, Zsuzsanna Callaerts-Vegh, Suresh Poovathingal, Teresa Prezzemolo
The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood–brain barrier. The recent identification and characterization of a small population of regulatory T
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Autoreactive CD8+ T cells are restrained by an exhaustion-like program that is maintained by LAG3 Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Stephanie Grebinoski, Qianxia Zhang, Anthony R. Cillo, Sasikanth Manne, Hanxi Xiao, Erin A. Brunazzi, Tracy Tabib, Carly Cardello, Christine G. Lian, George F. Murphy, Robert Lafyatis, E. John Wherry, Jishnu Das, Creg J. Workman, Dario A. A. Vignali
Impaired chronic viral and tumor clearance has been attributed to CD8+ T cell exhaustion, a differentiation state in which T cells have reduced and altered effector function that can be partially reversed upon blockade of inhibitory receptors. The role of the exhaustion program and transcriptional networks that control CD8+ T cell function and fate in autoimmunity is not clear. Here we show that intra-islet
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KSHV-encoded ORF45 activates human NLRP1 inflammasome Nat. Immunol. (IF 25.606) Pub Date : 2022-05-26 Xing Yang, Jingfan Zhou, Chengrong Liu, Yafei Qu, Weili Wang, Maggie Z. X. Xiao, Fanxiu Zhu, Zhenshan Liu, Qiming Liang
At steady state, the NOD-like receptor (NLR)-containing pyrin domain (PYD) (NLRP)1 inflammasome is maintained in an auto-inhibitory complex by dipeptidyl peptidases 8 and 9 (DPP8 and DPP9) and is activated by pathogen-encoded proteases after infection. Here, we showed that the open reading frame (ORF)45 protein of the Kaposi’s sarcoma-associated herpesvirus activated the human NLRP1 (hNLRP1) inflammasome
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Reply to: Hultström et al., Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19. Mannose-binding lectin genetics in COVID-19. Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Rosanna Asselta,Elvezia Maria Paraboschi,Matteo Stravalaci,Pietro Invernizzi,Paolo Bonfanti,Andrea Biondi,Isabel Pagani,Mattia Pedotti,Andrea Doni,Francesco Scavello,Sarah N Mapelli,Marina Sironi,Chiara Perucchini,Luca Varani,Milos Matkovic,Andrea Cavalli,Daniela Cesana,Pierangela Gallina,Nicoletta Pedemonte,Valeria Capurro,Nicola Clementi,Nicasio Mancini,Rafael Bayarri-Olmos,Peter Garred,Rino Rappuoli
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Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19. Nat. Immunol. (IF 25.606) Pub Date : 2022-05-27 Michael Hultström,Robert Frithiof,Jonathan Grip,Linnea Lindelöf,Olav Rooijackers,Sara Pigazzini,Mari Niemi,Mattia Cordioli,Lindo Nkambule,Tomislav Maricic,Kristina Nilsson Ekdahl,Bo Nilsson,Miklós Lipcsey,Hugo Zeberg,Oskar Eriksson
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New functions for basophils identified in kidney fibrosis Nat. Immunol. (IF 25.606) Pub Date : 2022-05-23 Haikuo Li, Benjamin D. Humphreys
Basophils are type 2 immune response cells, but they have also been associated with fibrosis. New data indicate that proximal tubule cells exert profibrotic effects by recruiting IL-6-producing basophils into the kidneys.
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Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis Nat. Immunol. (IF 25.606) Pub Date : 2022-05-12 Tomohito Doke, Amin Abedini, Daniel L. Aldridge, Ya-Wen Yang, Jihwan Park, Christina M. Hernandez, Michael S. Balzer, Rojesh Shrestra, Gaia Coppock, Juan M. Inclan Rico, Seung Yub Han, Junhyong Kim, Sheng Xin, Adrian M. Piliponsky, Marco Angelozzi, Veronique Lefebvre, Mark C. Siracusa, Christopher A. Hunter, Katalin Susztak
Inflammation is an important component of fibrosis but immune processes that orchestrate kidney fibrosis are not well understood. Here we apply single-cell sequencing to a mouse model of kidney fibrosis. We identify a subset of kidney tubule cells with a profibrotic-inflammatory phenotype characterized by the expression of cytokines and chemokines associated with immune cell recruitment. Receptor–ligand
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Reversing T cell immunity reveals the basis for T cell lineage fate determination Nat. Immunol. (IF 25.606) Pub Date : 2022-05-09
Switching the CD4 and CD8 coreceptor proteins encoded in Cd4 and Cd8 loci results in a reversed T cell immune system, with CD4+ cytotoxic T cells and CD8+ helper T cells. Thus, whichever coreceptor is encoded in Cd4 promotes a helper lineage fate, and whichever is encoded in Cd8 promotes a cytotoxic lineage fate.
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Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose Nat. Immunol. (IF 25.606) Pub Date : 2022-05-09 Yaniv Lustig, Tal Gonen, Lilac Meltzer, Mayan Gilboa, Victoria Indenbaum, Carmit Cohen, Sharon Amit, Hanaa Jaber, Ram Doolman, Keren Asraf, Carmit Rubin, Ronen Fluss, Ella Mendelson, Laurence Freedman, Gili Regev-Yochay, Yitshak Kreiss
As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were
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Dual ligand engagement for noncanonical inflammasome activation Nat. Immunol. (IF 25.606) Pub Date : 2022-04-29 Zhang-Hua Yang, Jiahuai Han
The activation of the noncanonical NLRP3 inflammasome can be elicited by the interaction and interdependent activation of caspase-11 and NLRP3 that follows coincident cytosolic detection of lipopolysaccharide and bacterial mRNA from live Gram-negative bacteria.
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ILC1s control leukemia stem cell fate and limit development of AML Nat. Immunol. (IF 25.606) Pub Date : 2022-04-29 Zhenlong Li, Rui Ma, Shoubao Ma, Lei Tian, Ting Lu, Jianying Zhang, Bethany L. Mundy-Bosse, Bin Zhang, Guido Marcucci, Michael A. Caligiuri, Jianhua Yu
Type I innate lymphoid cells (ILC1s) are critical regulators of inflammation and immunity in mammalian tissues. However, their function in cancer is mostly undefined. Here, we show that a high density of ILC1s induces leukemia stem cell (LSC) apoptosis in mice. At a lower density, ILC1s prevent LSCs from differentiating into leukemia progenitors and promote their differentiation into non-leukemic cells
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TCF-1: a maverick in T cell development and function Nat. Immunol. (IF 25.606) Pub Date : 2022-04-29 Fotini Gounari, Khashayarsha Khazaie
The T cell-specific DNA-binding protein TCF-1 is a central regulator of T cell development and function along multiple stages and lineages. Because it interacts with β-catenin, TCF-1 has been classically viewed as a downstream effector of canonical Wnt signaling, although there is strong evidence for β-catenin-independent TCF-1 functions. TCF-1 co-binds accessible regulatory regions containing or lacking
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Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome Nat. Immunol. (IF 25.606) Pub Date : 2022-04-29 Julien Moretti, Baosen Jia, Zachary Hutchins, Soumit Roy, Hilary Yip, Jiahui Wu, Meimei Shan, Samie R. Jaffrey, Jörn Coers, J. Magarian Blander
Caspase-11 detection of intracellular lipopolysaccharide (LPS) from invasive Gram-negative bacteria mediates noncanonical activation of the NLRP3 inflammasome. While avirulent bacteria do not invade the cytosol, their presence in tissues necessitates clearance and immune system mobilization. Despite sharing LPS, only live avirulent Gram-negative bacteria activate the NLRP3 inflammasome. Here, we found
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Creating ATP via creatine kinase B for NLRP3 activation Nat. Immunol. (IF 25.606) Pub Date : 2022-04-28 Juliana E. Toller-Kawahisa, Luke A. J. O’Neill
A role for mitochondrial ATP that leads to phosphocreatine and the subsequent generation of cytosolic ATP via creatine kinase B is now proposed in the activation of the NLRP3 inflammasome.
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CD66b−CD64dimCD115− cells in the human bone marrow represent neutrophil-committed progenitors Nat. Immunol. (IF 25.606) Pub Date : 2022-04-28 Federica Calzetti, Giulia Finotti, Nicola Tamassia, Francisco Bianchetto-Aguilera, Monica Castellucci, Stefania Canè, Silvia Lonardi, Chiara Cavallini, Alessandro Matte, Sara Gasperini, Ilaria Signoretto, Fabio Benedetti, Massimiliano Bonifacio, William Vermi, Stefano Ugel, Vincenzo Bronte, Cristina Tecchio, Patrizia Scapini, Marco A. Cassatella
Here we report the identification of human CD66b−CD64dimCD115− neutrophil-committed progenitor cells (NCPs) within the SSCloCD45dimCD34+ and CD34dim/− subsets in the bone marrow. NCPs were either CD45RA+ or CD45RA−, and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b+ neutrophils in both in vitro differentiation
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Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation Nat. Immunol. (IF 25.606) Pub Date : 2022-04-28 Leah K. Billingham, Joshua S. Stoolman, Karthik Vasan, Arianne E. Rodriguez, Taylor A. Poor, Marten Szibor, Howard T. Jacobs, Colleen R. Reczek, Aida Rashidi, Peng Zhang, Jason Miska, Navdeep S. Chandel
The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the NLRP3 inflammasome through several mechanisms including generation of mitochondrial reactive oxygen species (ROS). Here, we report that mitochondrial electron transport chain (ETC) complex I, II, III and V inhibitors
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Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus Nat. Immunol. (IF 25.606) Pub Date : 2022-04-29 Miho Shinzawa, E. Ashley Moseman, Selamawit Gossa, Yasuko Mano, Abhisek Bhattacharya, Terry Guinter, Amala Alag, Xiongfong Chen, Maggie Cam, Dorian B. McGavern, Batu Erman, Alfred Singer
T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such
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LAG3 disrupts the TCR signal by local acidification Nat. Immunol. (IF 25.606) Pub Date : 2022-04-27 Claire Hivroz
LAG3 interferes with TCR signaling by lowering the pH in the vicinity of the TCR and inducing dissociation of the key signaling kinase Lck from the co-receptors CD8 and CD4.
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The ImmGen consortium OpenSource T cell project. Nat. Immunol. (IF 25.606) Pub Date : 2022-05-01 David Zemmour,Ananda Goldrath,Mitchell Kronenberg,Joonsoo Kang,Christophe Benoist
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T cells in COVID-19 — the kids are all right Nat. Immunol. (IF 25.606) Pub Date : 2022-04-21 John D. Altman
Thomas and colleagues describe how multiple mRNA vaccine boosters, with or without natural SARS-CoV-2 infection, shape T cell immunity.
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T cell memories of past divisions Nat. Immunol. (IF 25.606) Pub Date : 2022-04-21 Lorenz Kretschmer, Veit R. Buchholz
A genetic recorder of T cell replicative history identifies fewer accumulated divisions in a subset of CD8+ central memory T cells that shows stem-cell-like quiescence and superior recall capacity.
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Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling Nat. Immunol. (IF 25.606) Pub Date : 2022-04-21 Alejandro Moro, Zhen Gao, Lily Wang, Aixin Yu, Sunnie Hsiung, Yuguang Ban, Aimin Yan, Corneliu M. Sologon, X. Steven Chen, Thomas R. Malek
Regulatory T (Treg) cells require (interleukin-2) IL-2 for their homeostasis by affecting their proliferation, survival and activation. Here we investigated transcriptional and epigenetic changes after acute, periodic and persistent IL-2 receptor (IL-2R) signaling in mouse peripheral Treg cells in vivo using IL-2 or the long-acting IL-2-based biologic mouse IL-2–CD25. We show that initially IL-2R-dependent
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PD-L1–PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection Nat. Immunol. (IF 25.606) Pub Date : 2022-04-18 Joseph A. Perry, Lindsey Shallberg, Joseph T. Clark, Jodi A. Gullicksrud, Jonathan H. DeLong, Bonnie B. Douglas, Andrew P. Hart, Zachary Lanzar, Keenan O’Dea, Christoph Konradt, Jeongho Park, Juhi R. Kuchroo, Daniel Grubaugh, Arielle Glatman Zaretsky, Igor E. Brodsky, Rene de Waal Malefyt, David A. Christian, Arlene H. Sharpe, Christopher A. Hunter
Phenotypic and transcriptional profiling of regulatory T (Treg) cells at homeostasis reveals that T cell receptor activation promotes Treg cells with an effector phenotype (eTreg) characterized by the production of interleukin-10 and expression of the inhibitory receptor PD-1. At homeostasis, blockade of the PD-1 pathway results in enhanced eTreg cell activity, whereas during infection with Toxoplasma gondii
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LAG3 associates with TCR–CD3 complexes and suppresses signaling by driving co-receptor–Lck dissociation Nat. Immunol. (IF 25.606) Pub Date : 2022-04-18 Clifford Guy, Diana M. Mitrea, Po-Chien Chou, Jamshid Temirov, Kate M. Vignali, Xueyan Liu, Hui Zhang, Richard Kriwacki, Marcel P. Bruchez, Simon C. Watkins, Creg J. Workman, Dario A. A. Vignali
LAG3 is an inhibitory receptor that is highly expressed on exhausted T cells. Although LAG3-targeting immunotherapeutics are currently in clinical trials, how LAG3 inhibits T cell function remains unclear. Here, we show that LAG3 moved to the immunological synapse and associated with the T cell receptor (TCR)-CD3 complex in CD4+ and CD8+ T cells, in the absence of binding to major histocompatibility
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Author Correction: Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization Nat. Immunol. (IF 25.606) Pub Date : 2022-04-13 Johannes U. Mayer,Kerry L. Hilligan,Jodie S. Chandler,David A. Eccles,Samuel I. Old,Rita G. Domingues,Jianping Yang,Greta R. Webb,Luis Munoz-Erazo,Evelyn J. Hyde,Kirsty A. Wakelin,Shiau-Choot Tang,Sally C. Chappell,Sventja von Daake,Frank Brombacher,Charles R. Mackay,Alan Sher,Roxane Tussiwand,Lisa M. Connor,David Gallego-Ortega,Dragana Jankovic,Graham Le Gros,Matthew R. Hepworth,Olivier Lamiable,Franca
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Publisher Correction: Tcf1 preprograms the mobilization of glycolysis in central memory CD8+ T cells during recall responses Nat. Immunol. (IF 25.606) Pub Date : 2022-04-12 Qiang Shan,Shengen Shawn Hu,Shaoqi Zhu,Xia Chen,Vladimir P. Badovinac,Weiqun Peng,Chongzhi Zang,Hai-Hui Xue
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Replicative history marks transcriptional and functional disparity in the CD8+ T cell memory pool Nat. Immunol. (IF 25.606) Pub Date : 2022-04-07 Kaspar Bresser, Lianne Kok, Arpit C. Swain, Lisa A. King, Laura Jacobs, Tom S. Weber, Leïla Perié, Ken R. Duffy, Rob J. de Boer, Ferenc A. Scheeren, Ton N. Schumacher
Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8+ memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically ‘record’
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Transcriptional state and function of CD8+ memory T cells is linked to past proliferation Nat. Immunol. (IF 25.606) Pub Date : 2022-04-07
A new genetic ‘recorder’ of long-term cell proliferation revealed substantial heterogeneity in the division history of central memory CD8+ T cells. Importantly, the extent of past proliferation was related to distinct transcriptional features and re-expansion potential, highlighting an unappreciated division of labor within the central memory T cell pool.
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SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells Nat. Immunol. (IF 25.606) Pub Date : 2022-04-05 Anastasia A. Minervina, Mikhail V. Pogorelyy, Allison M. Kirk, Jeremy Chase Crawford, E. Kaitlynn Allen, Ching-Heng Chou, Robert C. Mettelman, Kim J. Allison, Chun-Yang Lin, David C. Brice, Xun Zhu, Kasi Vegesana, Gang Wu, Sanchit Trivedi, Pratibha Kottapalli, Daniel Darnell, Suzanne McNeely, Scott R. Olsen, Stacey Schultz-Cherry, Jeremie H. Estepp, Maureen A. McGargill, Joshua Wolf, Paul G. Thomas
Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile S