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  • Immune metabolism in PD-1 blockade-based cancer immunotherapy
    Int. Immunol. (IF 3.519) Pub Date : 2020-07-05
    Alok Kumar; Kenji Chamoto

    Energy metabolism plays an important role in proliferating cells. Recent reports indicate that metabolic regulation or metabolic products can control immune cell differentiation, fate and reactions. Cancer immunotherapy based on blockade of programmed cell death protein 1 (PD-1) has been used worldwide, but a significant fraction of patients remain unresponsive. Therefore, clarifying the mechanisms

    更新日期:2020-07-05
  • The relationship between CD4+ follicular helper T cells and CD8+ resident memory T cells: sisters or distant cousins?
    Int. Immunol. (IF 3.519) Pub Date : 2020-07-03
    Changwei Peng; Stephen C Jameson

    Independent studies over the last decade have characterized the properties of non-circulating CD8+ “resident” memory T cells (TRM), which offer barrier protective immunity in non-lymphoid tissues and CD4+ follicular helper T cells (TFH), which mediate B cell help in lymphoid sites. Despite their very different biological roles in the immune system, intriguing parallels have been noted between the trafficking

    更新日期:2020-07-05
  • Autosomal recessive complete STAT1 deficiency caused by compound heterozygous intronic mutations
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-30
    Sonoko Sakata; Miyuki Tsumura; Tadashi Matsubayashi; Shuhei Karakawa; Shunsuke Kimura; Moe Tamaura; Tsubasa Okano; Takuya Naruto; Yoko Mizoguchi; Reiko Kagawa; Shiho Nishimura; Kohsuke Imai; Tom Le Voyer; Jean-Laurent Casanova; Jacinta Bustamante; Tomohiro Morio; Osamu Ohara; Masao Kobayashi; Satoshi Okada

    Autosomal recessive (AR) complete signal transducer and activator of transcription 1 (STAT1) deficiency is an extremely rare primary immunodeficiency that causes life-threatening mycobacterial and viral infections. Only seven patients from five unrelated families with this disorder have been so far reported. All causal STAT1 mutations reported are exonic and homozygous. We studied a patient with susceptibility

    更新日期:2020-06-30
  • Introduction: Special Issue—Immunometabolism
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-22
    Heiichiro Udono; Atsushi Kumanogoh

    Cell metabolism can be defined as the anabolic and catabolic biochemical pathways that generate energy, supply building blocks for synthesis and enable the breakdown of complex molecules. Vast efforts have succeeded in delineating these processes in a huge number of cell types across the entire range of species. Many basic pathways are in fact shared across this range and by all cells within individuals

    更新日期:2020-06-26
  • Role of dendritic cell metabolic reprogramming in tumor immune evasion.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-25
    Michael P Plebanek,Michael Sturdivant,Nicholas C DeVito,Brent A Hanks

    The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of

    更新日期:2020-06-26
  • Danger-associated metabolic modifications during bacterial infection of macrophages.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-22
    Mariatou Dramé,Carmen Buchrieser,Pedro Escoll

    In this review, we propose that certain modifications in cellular metabolism might function as danger signals triggering inflammasome-mediated immune responses. We propose to call them danger-associated metabolic modifications (DAMMs). As intracellular bacteria can actively modulate macrophage metabolism for their benefit, infected host cells might sense bacteria-induced metabolic alterations and activate

    更新日期:2020-06-26
  • Amino acids: key sources for immunometabolites and immunotransmitters.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-08
    Michio Miyajima

    Immune-cell activation and functional plasticity are closely linked to metabolic reprogramming that is required to supply the energy and substrates for such dynamic transformations. During such processes, immune cells metabolize many kinds of molecules including nucleic acids, sugars and lipids, which is called immunometabolism. This review will mainly focus on amino acids and their derivatives among

    更新日期:2020-06-26
  • Tet DNA demethylase is required for plasma cell differentiation by controlling expression levels of IRF4
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-25
    Kentaro Fujii; Shinya Tanaka; Takanori Hasegawa; Masashi Narazaki; Atsushi Kumanogoh; Haruhiko Koseki; Tomohiro Kurosaki; Wataru Ise

    Antibodies produced by plasma cells are critical for protection from infection. It has been demonstrated that global epigenetic modification, such as changes in DNA methylation, occurs during differentiation of plasma cells from B cells. However, the precise mechanisms by which DNA methylation controls plasma cell differentiation are not fully understood. We examined the effect of deficiency of DNA

    更新日期:2020-06-25
  • The impact of metabolites derived from the gut microbiota on immune regulation and diseases.
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-20
    Hiroshi Ohno

    Gut microbiota strongly impacts the physiology and pathology in the host. To understand the complex interactions between host and gut microbiota, an “integrated omics” approach has been employed, where exhaustive analyses for the different layers of cellular functions, such as epigenomics, transcriptomics and metabolomics, in addition to metagenomics, are combined. With this approach, the mechanisms

    更新日期:2020-06-23
  • Impact of multiple hits with cognate antigen on memory CD8+ T cell fate.
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-07
    Shiki Takamura

    Antigen-driven activation of CD8+ T cells results in the development of a robust anti-pathogen response and ultimately leads to the establishment of long-lived memory T cells. During the primary response, CD8+ T cells interact multiple times with cognate antigen on distinct types of antigen-presenting cells. The timing, location and context of these antigen encounters significantly impact the differentiation

    更新日期:2020-06-07
  • Stereotyped B-cell response that counteracts antigenic variation of influenza viruses.
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-06
    Keisuke Tonouchi,Yu Adachi,Saya Moriyama,Kaori Sano,Koshiro Tabata,Keigo Ide,Haruko Takeyama,Tadaki Suzuki,Yoshimasa Takahashi

    Influenza A subtypes are categorized into group 1 and group 2 based on hemagglutinin (HA) sequence. Owing to the phylogenetic distance of HAs in different groups, antibodies that bind multiple HA subtypes across different groups are extremely rare. In this study, we demonstrated that an immunization with acid-treated HA antigen elicits germinal center (GC) B cells that bind multiple HA subtypes in

    更新日期:2020-06-06
  • Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity.
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-04
    Hisataka Kobayashi,Aki Furusawa,Adrian Rosenberg,Peter L Choyke

    Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy that directly kills cancer cells as well as producing a therapeutic host immune response. Conventional immunotherapies, such as immune-activating cytokine therapy, checkpoint inhibition, engineered T-cells and suppressor cell depletion, do not directly destroy cancer cells, but rely exclusively on activating the

    更新日期:2020-06-04
  • Lung fibroblasts produce interleukin-33 in response to stimulation by retinoblastoma-binding protein 9 via production of prostaglandin E2.
    Int. Immunol. (IF 3.519) Pub Date : 2020-06-03
    Takumi Adachi,Koubun Yasuda,Taichiro Muto,Satoshi Serada,Tomohiro Yoshimoto,Ken J Ishii,Etsushi Kuroda,Kimi Araki,Masaki Ohmuraya,Tetsuji Naka,Kenji Nakanishi

    Intestinal nematode infection induces pulmonary eosinophilia via interleukin (IL)-33, although the mechanism of pulmonary IL-33 induction remains unclear. Because nematode migration damages lungs, we speculated that lung-derived damage-associated molecular patterns (DAMPs) possess an IL-33-inducing activity (IL33ia). Indeed, intranasal administration of a lung extract induced IL-33 production in lungs

    更新日期:2020-06-03
  • In This Issue
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-30

    Keratinocytes produce cytokines and participate in immune responses and skin healing. Poly(I:C) is a ligand for TLR3 that induces the production of IL-8 in skin and promotes wound repair. Bee venom (BV) has many effects on skin, and Nakashima et al. show that BV synergizes with various TLR ligands to enhance the IL-8 production in HaCaT cells (a human keratinocyte cell line). This is especially marked

    更新日期:2020-05-30
  • Pivotal role of carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-16
    Junta Nasu,Tomofumi Uto,Tomohiro Fukaya,Hideaki Takagi,Takehito Fukui,Noriaki Miyanaga,Yotaro Nishikawa,Sho Yamasaki,Yoshihiro Yamashita,Katsuaki Sato

    C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) characteristic with a carbohydrate recognition domain (CRD) in the extracellular portion, mediate crucial cellular functions upon recognition of glycosylated pathogens and self-glycoproteins. CLEC4A is the only classical CLR that possesses an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM), which possibly transduces

    更新日期:2020-05-16
  • Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-05
    Yusuke Takada,Daisuke Kamimura,Jing-Jing Jiang,Haruka Higuchi,Daiki Iwami,Kiyohiko Hotta,Yuki Tanaka,Mitsutoshi Ota,Madoka Higuchi,Saori Nishio,Tatsuya Atsumi,Nobuo Shinohara,Yoshihiro Matsuno,Takahiro Tsuji,Tatsu Tanabe,Hajime Sasaki,Naoya Iwahara,Masaaki Murakami

    Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation, and about 25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this

    更新日期:2020-05-05
  • Impaired mucociliary motility enhances antigen-specific nasal IgA immune responses to a cholera toxin-based nasal vaccine.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-29
    Huangwenxian Lan,Hidehiko Suzuki,Takahiro Nagatake,Koji Hosomi,Koji Ikegami,Mitsutoshi Setou,Jun Kunisawa

    Nasal mucosal tissues are equipped with physical barriers, mucus and cilia, on their surface. The mucus layer captures inhaled materials, and the cilia remove the inhaled materials from the epithelial layer by asymmetrical beating. The effect of nasal physical barriers on the vaccine efficacy remains to be investigated. Tubulin tyrosine ligase-like family member 1 (Ttll1) is an essential enzyme for

    更新日期:2020-04-29
  • The origin, fate and function of macrophages in the peripheral nervous system - an update.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-23
    Lukas Amann,Marco Prinz

    The field of macrophage biology has made enormous progress over recent years. This was triggered by the advent of several new techniques such as the establishment of Cre/loxP-based transgenic mouse models that allowed for the first time to delineate the ontogeny and function of specific macrophage populations across many tissues. In addition, the introduction of new high-throughput technologies like

    更新日期:2020-04-23
  • Hide and seek: interplay between influenza viruses and B cells.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-18
    Masayuki Kuraoka,Yu Adachi,Yoshimasa Takahashi

    Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against

    更新日期:2020-04-18
  • Lipid mediators and sterile inflammation in ischemic stroke.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-17
    Akari Nakamura,Kento Otani,Takashi Shichita

    Stroke is one of the major causes of lethality and disability, yet few effective therapies have been established for ischemic stroke. Inflammation in the ischemic brain is induced by the infiltration and subsequent activation of immune cells. Loss of cerebral blood flow and ischemic brain-cell death trigger the activation of infiltrating immune cells and drastic changes in the lipid content of the

    更新日期:2020-04-17
  • Citrullinated fibrinogen is a target of autoantibodies in interstitial lung disease in mice with collagen-induced arthritis.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-02
    Tomomi Sato,Hiroki Satooka,Satoko Ichioka,Yoshihiro Maruo,Takako Hirata

    Interstitial lung disease (ILD) is a very common and lethal complication of rheumatoid arthritis (RA), yet its pathogenesis is not well understood, in part due to the lack of adequate animal models. Although collagen-induced arthritis (CIA) is the most widely used animal model for RA, the lung involvement occurring in this model has scarcely been studied. To evaluate the suitability of CIA as a model

    更新日期:2020-04-02
  • Diversity of energy metabolism in immune responses regulated by micro-organisms and dietary nutrition
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-27
    Koji Hosomi; Jun Kunisawa

    Immune metabolism has been recognized as a new paradigm in the regulation of host immunity. In the environment, there are many micro-organisms including pathogenic and non-pathogenic and/or beneficial ones. Immune cells exhibit various responses against different types of microbes, which seem to be associated with changes in energy metabolism. In addition, dietary nutrition influences host metabolism

    更新日期:2020-03-27
  • Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-27
    Haruka Higuchi,Daisuke Kamimura,Jing-Jing Jiang,Toru Atsumi,Daiki Iwami,Kiyohiko Hotta,Hiroshi Harada,Yusuke Takada,Hiromi Kanno-Okada,Kanako C Hatanaka,Yuki Tanaka,Nobuo Shinohara,Masaaki Murakami

    International Immunology, Volume 32, Issue 5, 1 May 2020, Pages 335–346, https://doi.org/10.1093/intimm/dxaa003

    更新日期:2020-03-27
  • The spectrum of macrophage activation by immunometabolism
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-16
    Sujin Kang; Atsushi Kumanogoh

    Macrophages are heterogeneous and plastic, and play several diverse functions in immune responses. Emerging data provide evidence of multiple roles for metabolic pathways in the control of macrophage effector functions. The diverse functions of macrophages are categorized into two main subsets: classical activated macrophages (M1) and alternative activated macrophages (M2). M1 macrophages secrete pro-inflammatory

    更新日期:2020-03-16
  • Sestrin3 enhances macrophage-mediated generation of T helper 1 and T helper 17 cells in a mouse colitis model.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-10
    Liuqing Ge,Min Xu,Steven R Brant,Shaoping Liu,Chengliang Zhu,Jian Shang,Qiu Zhao,Feng Zhou

    Intestinal macrophages participate in the pathogenesis of inflammatory bowel diseases (IBDs) through secreting pro-inflammatory and tissue-damaging factors as well as inducing the differentiation of T helper 1 (Th1) and T helper 17 (Th17) cells. Elucidating the regulatory mechanisms of intestinal macrophage activity in IBDs is important for developing new therapeutic approaches. In the current study

    更新日期:2020-03-10
  • Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-09
    Yurina Miyajima,Kafi N Ealey,Yasutaka Motomura,Miho Mochizuki,Natsuki Takeno,Motoko Yanagita,Aris N Economides,Manabu Nakayama,Haruhiko Koseki,Kazuyo Moro

    Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is

    更新日期:2020-03-09
  • Metabolic and immunologic control of intestinal cell function by mTOR
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-06
    Stephanie D Fritsch; Thomas Weichhart

    The intestinal epithelium is one of the most quickly dividing tissues in our body, combining the absorptive advantages of a single layer with the protection of a constantly renewing barrier. It is continuously exposed to nutrients and commensal bacteria as well as microbial and host-derived metabolites, but also to hazards such as pathogenic bacteria and toxins. These environmental cues are sensed

    更新日期:2020-03-06
  • Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-04
    Yue Yang,Shigenori Nagai,Siwen Kang,Yulong Xia,Yohei Kawano,Kensuke Miyake,Hajime Karasuyama,Miyuki Azuma

    The sublingual mucosa (SLM) in the oral cavity is utilized as the site for sublingual immunotherapy to induce tolerance against allergen. We previously reported that CD206+ round-type macrophage-like cells were induced in the SLM after repeated antigen (e.g., cedar pollen or FITC)-painting. In this study, we examined the phenotypic and functional properties of CD206+ cells induced by repeated FITC-painting

    更新日期:2020-03-04
  • Repurposing the Psoriasis Drug Oxarol to an ointment adjuvant for the influenza vaccine.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-15
    Ryota Sato,Chieko Makino-Okamura,Quingshun Lin,Muing Wang,Jason Shoemaker,Tomohiro Kurosaki,Hidehiro Fukuyama

    Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the Psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from

    更新日期:2020-02-15
  • PD-1+ Tim3+ tumor-infiltrating CD8 T cells sustain the potential for IFN-γ production, but lose cytotoxic activity in ovarian cancer.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-03
    Masaaki Sawada,Kumiko Goto,Akiko Morimoto-Okazawa,Miya Haruna,Kei Yamamoto,Yoko Yamamoto,Satoshi Nakagawa,Kosuke Hiramatsu,Shinya Matsuzaki,Eiji Kobayashi,Atsunari Kawashima,Michinari Hirata,Kota Iwahori,Toshihiro Kimura,Yutaka Ueda,Tadashi Kimura,Hisashi Wada

    Persistent exposure to tumor antigens results in exhausted tumor-infiltrating T cells (TILs) that express the immune checkpoint molecules, PD-1 and Tim3, and lack anti-tumor immunity. To examine the exhausted status of TILs in ovarian cancer, the potential for cytokine production, proliferation and cytotoxicity by purified PD-1+ Tim3+ CD8 TILs was assessed. The production of IFN-γ and TNF-α by PD-1+

    更新日期:2020-02-03
  • Ubiquitination of IgG1 cytoplasmic tail modulates B-cell signalling and activation.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-01
    Tadahiro Kodama,Mika Hasegawa,Yui Sakamoto,Kei Haniuda,Daisuke Kitamura

    Upon antigen stimulation, IgG+ B cells rapidly proliferate and differentiate into plasma cells, which has been attributed to the characteristics of membrane-bound IgG (mIgG), but the underlying molecular mechanisms remain elusive. We have found that a part of mouse mIgG1 is ubiquitinated through the two responsible lysine residues (K378 and K386) in its cytoplasmic tail and this ubiquitination is augmented

    更新日期:2020-02-01
  • Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-08
    Hisamichi Naito,Tomohiro Iba,Nobuyuki Takakura

    The vast blood-vessel network of the circulatory system is crucial for maintaining bodily homeostasis, delivering essential molecules and blood cells, and removing waste products. Blood-vessel dysfunction and dysregulation of new blood-vessel formation are related to the onset and progression of many diseases including cancer, ischemic disease, inflammation and immune disorders. Endothelial cells (ECs)

    更新日期:2020-01-30
  • Physiology and pathology of T-cell aging.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-12
    Nagahiro Minato,Masakazu Hattori,Yoko Hamazaki

    Acquired immune function shows recognizable changes over time with organismal aging. These changes include T-cell dysfunction, which may underlie diminished resistance to infection and possibly various chronic age-associated diseases in the elderly. T-cell dysfunction may occur at distinct stages, from naive cells to the end stages of differentiation during immune responses. The thymus, which generates

    更新日期:2020-01-22
  • Phospholipase A2 from bee venom increases poly(I:C)-induced activation in human keratinocytes.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-20
    Akina Nakashima,Susumu Tomono,Tatsuya Yamazaki,Masanori Inui,Naoko Morita,Isao Ichimonji,Hidekazu Takagi,Fumiaki Nagaoka,Misako Matsumoto,Yasuhiko Ito,Takeshi Yanagishita,Kensuke Miyake,Daisuke Watanabe,Sachiko Akashi-Takamura

    Bee venom (BV) induces skin inflammation, characterized by erythema, blisters, edemas, pain and itching. Although BV has been found to have an inhibitory effect on toll-like receptors (TLRs), we here show that BV enhances keratinocyte responses to polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3. Our results revealed that the enhanced TLR activity was primarily induced by secretory phospholipase

    更新日期:2020-01-20
  • Clinical importance of the expression of CD4+CD8+ T cells in renal cell carcinoma.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-08
    Kentaro Nishida,Atsunari Kawashima,Takayuki Kanazawa,Yujiro Kidani,Tetsuya Yoshida,Michinari Hirata,Kei Yamamoto,Yoko Yamamoto,Masaaki Sawada,Ryo Kato,Taigo Kato,Koji Hatano,Takeshi Ujike,Kazutoshi Fujita,Motohide Uemura,Akiko Morimoto-Okazawa,Kota Iwahori,Makoto Yamasaki,Naganari Ohkura,Shimon Sakaguchi,Norio Nonomura,Yuichiro Doki,Hisashi Wada

    OBJECTIVE CD4+CD8+ T cells are expressed in some cancer patients including those with renal cell carcinoma (RCC). However, no reports have mentioned the clinical importance of this expression. We evaluated the expression of CD4+CD8+ T cells in patients with various cancer types to clarify clinical characteristics and prognostic importance significantly correlating with these T cells. METHODS Expression

    更新日期:2020-01-17
  • Deficiency of TGR5 exacerbates immune-mediated cholestatic hepatic injury by stabilizing the β-catenin destruction complex.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-08
    Jianhua Rao,Chao Yang,Shikun Yang,Hao Lu,Yuanchang Hu,Ling Lu,Feng Cheng,Xuehao Wang

    Intrahepatic cholestasis induced by drug toxicity may cause cholestatic hepatic injury (CHI) leading to liver fibrosis and cirrhosis. The G protein-coupled bile acid receptor 1 (TGR5) is a membrane receptor with well-known roles in the regulation of glucose metabolism and energy homeostasis. However, the role and mechanism of TGR5 in the context of inflammation during CHI remains unclear. Wild-type

    更新日期:2020-01-13
  • Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation.
    Int. Immunol. (IF 3.519) Pub Date : 2020-05-08
    Haruka Higuchi,Daisuke Kamimura,Jing-Jing Jiang,Toru Atsumi,Daiki Iwami,Kiyohiko Hotta,Hiroshi Harada,Yusuke Takada,Hiromi Kanno-Okada,Kanako C Hatanaka,Yuki Tanaka,Nobuo Shinohara,Masaaki Murakami

    Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found

    更新日期:2020-01-13
  • Biallelic variants/mutations of IL1RAP in patients with steroid-sensitive nephrotic syndrome.
    Int. Immunol. (IF 3.519) Pub Date : 2020-04-12
    Sou Niitsuma,Hiroki Kudo,Atsuo Kikuchi,Takaya Hayashi,Satoshi Kumakura,Shuhei Kobayashi,Yuko Okuyama,Naonori Kumagai,Tetsuya Niihori,Yoko Aoki,Takanori So,Ryo Funayama,Keiko Nakayama,Matsuyuki Shirota,Shuji Kondo,Shoji Kagami,Hiroyasu Tsukaguchi,Kazumoto Iijima,Shigeo Kure,Naoto Ishii

    Nephrotic syndrome (NS) is a renal disease characterized by severe proteinuria and hypoproteinemia. Although several single-gene mutations have been associated with steroid-resistant NS, causative genes for steroid-sensitive NS (SSNS) have not been clarified. While seeking to identify causative genes associated with SSNS by whole-exome sequencing, we found compound heterozygous variants/mutations (c

    更新日期:2019-12-24
  • Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-07
    Yu-Hsien Lin,Satoko Tahara-Hanaoka,Kei Nagai,Soichiro Yoshikawa,Masato Kubo,Shiro Shibayama,Hajime Karasuyama,Akira Shibuya

    Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcεRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater

    更新日期:2019-11-01
  • Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-07
    Masashi Tachibana,Nobumasa Watanabe,Yuzo Koda,Yukako Oya,Osamu Kaminuma,Kazufumi Katayama,Zifei Fan,Fuminori Sakurai,Kenji Kawabata,Takachika Hiroi,Hiroyuki Mizuguchi

    IL-10 is an immune regulatory cytokine and its genetic defect leads to gastrointestinal inflammation in humans and mice. Moreover, the IL-23/Th17 axis is known to be involved in these inflammatory disorders. IL-17A, a representative cytokine produced by Th17 cells, has an important role for the pathological process of inflammatory diseases. However, the precise function of IL-17A in inflammatory bowel

    更新日期:2019-11-01
  • Synergistic effect of IgG4 antibody and CTLs causes tissue inflammation in IgG4-related disease.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-07
    Takanori Sasaki,Taiki Yajima,Tatsuro Shimaoka,Shuhei Ogawa,Takashi Saito,Kunihiro Yamaoka,Tsutomu Takeuchi,Masato Kubo

    IgG4-related disease (IgG4-RD) is characterized by multi-organ irreversible damage resulting from tissue-specific infiltration of IgG4+ plasma cells and cytotoxic T lymphocytes (CTLs). However, whether IgG4 antibody contributes to the inflammation remains unclear. In this study, we established a mouse model that enabled us to evaluate the pathogenic function of IgG4 antibodies in response to a tissue-specific

    更新日期:2019-11-01
  • ZBP1 governs the inflammasome-independent IL-1α and neutrophil inflammation that play a dual role in anti-influenza virus immunity.
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-07
    Masatoshi Momota,Patrick Lelliott,Atsuko Kubo,Takato Kusakabe,Kouji Kobiyama,Etsushi Kuroda,Yumiko Imai,Shizuo Akira,Cevayir Coban,Ken J Ishii

    Influenza A virus (IAV) triggers the infected lung to produce IL-1 and recruit neutrophils. Unlike IL-1β, however, little is known about IL-1α in terms of its mechanism of induction, action and physiological relevance to the host immunity against IAV infection. In particular, whether Z-DNA-binding protein 1 (ZBP1), a key molecule for IAV-induced cell death, is involved in the IL-1α induction, neutrophil

    更新日期:2019-11-01
  • Heterogeneous subsets of B-lineage regulatory cells (Breg cells).
    Int. Immunol. (IF 3.519) Pub Date : 2020-03-07
    Yoshihiro Baba,Yuichi Saito,Yasuaki Kotetsu

    B cells represent a key cellular component of humoral immunity. Besides antigen presentation and antibody production, B cells also play a role in immune regulation and induction of tolerance through several mechanisms. Our understanding of B-lineage cells with regulatory ability has been revolutionized by the delineation of heterogeneous subsets of these cells. Specific environmental signals may further

    更新日期:2019-11-01
  • IgG immune complexes with Staphylococcus aureus protein A enhance osteoclast differentiation and bone resorption by stimulating Fc receptors and TLR2.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Asana Kamohara,Hirohito Hirata,Xianghe Xu,Makoto Shiraki,Sakuo Yamada,Jing-Qi Zhang,Toshio Kukita,Kenji Toyonaga,Hiromitsu Hara,Yasuteru Urano,Yoshio Yamashita,Hiroshi Miyamoto,Akiko Kukita

    Staphylococcus aureus is a main pathogen of osteomyelitis and protein A is a virulence factor with high affinity for IgG. In this study, we investigated whether S. aureus affects the differentiation and bone resorption of osteoclasts through the IgG-binding capacity of protein A. Staphylococcus aureus pre-treated with serum or IgG showed marked enhancement in osteoclastogenesis and bone resorption

    更新日期:2019-11-01
  • Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Ichiro Takahashi,Koji Hosomi,Takahiro Nagatake,Hirokazu Toubou,Daiki Yamamoto,Ikue Hayashi,Yosuke Kurashima,Shintaro Sato,Naoko Shibata,Yoshiyuki Goto,Fumito Maruyama,Ichiro Nakagawa,Asaomi Kuwae,Akio Abe,Jun Kunisawa,Hiroshi Kiyono

    Accumulating evidence has revealed that lymphoid tissue-resident commensal bacteria (e.g. Alcaligenes spp.) survive within dendritic cells. We extended our previous study by investigating microbes that persistently colonize colonic macrophages. 16S rRNA-based metagenome analysis using DNA purified from murine colonic macrophages revealed the presence of Stenotrophomonas maltophilia. The in situ intracellular

    更新日期:2019-11-01
  • Suppressive role of PPARγ in the IgE-dependent activation of mast cells.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Kazuki Nagata,Kazumi Kasakura,Ryosuke Miura,Takuya Yashiro,Chiharu Nishiyama

    Mast cells (MCs) play a central role in IgE-dependent immune responses. PPARγ is a nuclear receptor that is essential for adipocyte differentiation and insulin sensitivity. Although PPARγ is expressed in activated MCs, the effect of PPARγ suppression in IgE-mediated activation of MCs is largely unknown. In the current study, we evaluated the effect of PPARγ knockdown on the function of IgE plus antigen

    更新日期:2019-11-01
  • Tissue-specific autoimmunity controlled by Aire in thymic and peripheral tolerance mechanisms.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Minoru Matsumoto,Koichi Tsuneyama,Junko Morimoto,Kazuyoshi Hosomichi,Mitsuru Matsumoto,Hitoshi Nishijima

    Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated

    更新日期:2019-11-01
  • Characterization of the developmental landscape of murine RORγt+ iNKT cells.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Jihene Klibi,Shamin Li,Ludivine Amable,Claudine Joseph,Stéphane Brunet,Marc Delord,Veronique Parietti,Jean Jaubert,Julien Marie,Saoussen Karray,Gerard Eberl,Bruno Lucas,Antoine Toubert,Kamel Benlagha

    Invariant natural killer T (iNKT) cells expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events accompanying their normal thymic development. We found that RORγt+ iNKT cells have

    更新日期:2019-11-01
  • Phospho-Ser727 triggers a multistep inactivation of STAT3 by rapid dissociation of pY705-SH2 through C-terminal tail modulation.
    Int. Immunol. (IF 3.519) Pub Date : 2020-02-07
    Junhao Yang,Hiroyuki Kunimoto,Bumpei Katayama,Hong Zhao,Takashi Shiromizu,Lingyu Wang,Toshiyuki Ozawa,Takeshi Tomonaga,Daisuke Tsuruta,Koichi Nakajima

    Signal transducer and activator of transcription 3 (STAT3) is involved in many biological processes, including immunity and cancer. STAT3 becomes phosphorylated at Tyr705 and Ser727 on IL-6 stimulation. Phospho-Tyr705 (pY705) stabilizes the STAT3 dimer with reciprocal interactions between pY705 and the SH2 of the other molecule and phospho-Ser727 (pS727) accelerates pY705 dephosphorylation. We study

    更新日期:2019-11-01
  • Matrix metalloproteinases cleave membrane-bound PD-L1 on CD90+ (myo-)fibroblasts in Crohn's disease and regulate Th1/Th17 cell responses.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Jose E Aguirre,Ellen J Beswick,Carl Grim,Gabriela Uribe,Marissa Tafoya,Gabriela Chacon Palma,Von Samedi,Rohini McKee,Romain Villeger,Yuriy Fofanov,Yingzi Cong,Gregory Yochum,Walter Koltun,Don Powell,Irina V Pinchuk

    Increased T helper (Th)1/Th17 immune responses are a hallmark of Crohn's disease (CD) immunopathogenesis. CD90+ (myo-)fibroblasts (MFs) are abundant cells in the normal (N) intestinal mucosa contributing to mucosal tolerance via suppression of Th1 cell activity through cell surface membrane-bound PD-L1 (mPD-L1). CD-MFs have a decreased level of mPD-L1. Consequently, mPD-L1-mediated suppression of Th1

    更新日期:2019-11-01
  • A suppressive oligodeoxynucleotide expressing TTAGGG motifs modulates cellular energetics through the mTOR signaling pathway.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Volkan Yazar,Gizem Kilic,Ozlem Bulut,Tugce Canavar Yildirim,Fuat C Yagci,Gamze Aykut,Dennis M Klinman,Mayda Gursel,Ihsan Gursel

    Immune-mediated inflammation must be down-regulated to facilitate tissue remodeling during homeostatic restoration of an inflammatory response. Uncontrolled or over-exuberant immune activation can cause autoimmune diseases, as well as tissue destruction. A151, the archetypal example of a chemically synthesized suppressive oligodeoxynucleotide (ODN) based on repetitive telomere-derived TTAGGG sequences

    更新日期:2019-11-01
  • DOCK family proteins: key players in immune surveillance mechanisms.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Kazufumi Kunimura,Takehito Uruno,Yoshinori Fukui

    Dedicator of cytokinesis (DOCK) proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in other GEFs, they mediate the GTP-GDP exchange reaction through the DOCK homology region-2 (DHR-2) domain. In mammals, this family consists of 11 members

    更新日期:2019-11-01
  • Analysis of intestinal immunity and flora in a collagen-induced mouse arthritis model: differences during arthritis progression.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Nobuhito Nemoto,Yuji Takeda,Hidetoshi Nara,Akemi Araki,Md Yeashin Gazi,Yuya Takakubo,Yasushi Naganuma,Michiaki Takagi,Hironobu Asao

    Intestinal immunity and flora are reported to be associated with the onset of rheumatoid arthritis. However, differences in the intestinal immunity and flora dynamics between the initial peak and relapse of arthritis have not been investigated. Here we analyzed the lymphocyte populations in different lymphoid tissues, the IgA in feces, and the intestinal flora at the initial peak and the relapse phase

    更新日期:2019-11-01
  • Self-reactive and polyreactive B cells are generated and selected in the germinal center during γ-herpesvirus infection.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Shuhei Sakakibara,Teruhito Yasui,Hideyuki Jinzai,Kristy O'donnell,Chao-Yuan Tsai,Takeharu Minamitani,Kazuya Takeda,Gabrielle T Belz,David M Tarlinton,Hitoshi Kikutani

    Immune responses against certain viruses are accompanied by auto-antibody production although the origin of these infection-associated auto-antibodies is unclear. Here, we report that murine γ-herpesvirus 68 (MHV68)-induced auto-antibodies are derived from polyreactive B cells in the germinal center (GC) through the activity of short-lived plasmablasts. The analysis of recombinant antibodies from MHV68-infected

    更新日期:2019-11-01
  • Distinct roles of BCNP1 in B-cell development and activation.
    Int. Immunol. (IF 3.519) Pub Date : 2020-01-09
    Rongjian Hong,Nannan Lai,Ermeng Xiong,Rika Ouchida,Jiping Sun,Yang Zhou,Yue Tang,Masaki Hikida,Takeshi Tsubata,Masatoshi Tagawa,Yanqing Wang,Ji-Yang Wang

    B-cell novel protein 1 (BCNP1) has recently been identified as a new B-cell receptor (BCR) signaling molecule but its physiological function remains unknown. Here, we demonstrate that mice deficient in BCNP1 exhibit impaired B-cell maturation and a reduction of B-1a cells. BCNP1-deficient spleen B cells show enhanced survival, proliferation and Ca2+ influx in response to BCR cross-linking as compared

    更新日期:2019-11-01
  • Metabolic adaptation to glycolysis is a basic defense mechanism of macrophages for Mycobacterium tuberculosis infection.
    Int. Immunol. (IF 3.519) Pub Date : 2019-11-08
    Mayuko Osada-Oka,Nobuhito Goda,Hiroyuki Saiga,Masahiro Yamamoto,Kiyoshi Takeda,Yuriko Ozeki,Takehiro Yamaguchi,Tomoyoshi Soga,Yu Tateishi,Katsuyuki Miura,Daisuke Okuzaki,Kazuo Kobayashi,Sohkichi Matsumoto

    Macrophages are major components of tuberculosis (TB) granulomas and are responsible for host defenses against the intracellular pathogen, Mycobacterium tuberculosis. We herein showed the strong expression of hypoxia-inducible factor-1α (HIF-1α) in TB granulomas and more rapid death of HIF-1α-conditional knockout mice than wild-type (WT) mice after M. tuberculosis infection. Although interferon-γ (IFN-γ)

    更新日期:2019-11-01
  • Broad and systemic immune-modulating capacity of plant-derived dsRNA.
    Int. Immunol. (IF 3.519) Pub Date : 2019-11-08
    Takara Hajake,Keita Matsuno,Dacquin M Kasumba,Haruka Oda,Moe Kobayashi,Nao Miyata,Madoka Shinji,Amane Kogure,Nodoka Kasajima,Masatoshi Okamatsu,Yoshihiro Sakoda,Hiroki Kato,Takashi Fujita

    Double-stranded RNA (dsRNA) is well characterized as an inducer of anti-viral interferon responses. We previously reported that dsRNA extracted from a specific edible plant possesses an immune-modulating capacity to confer, in mice, resistance against respiratory viruses, including the H1N1 strain of the influenza A virus (IAV). We report here that the systemic immune-activating capacity of the plant-derived

    更新日期:2019-11-01
  • Intestinal dysbiosis mediates experimental autoimmune pancreatitis via activation of plasmacytoid dendritic cells.
    Int. Immunol. (IF 3.519) Pub Date : 2019-11-08
    Ken Kamata,Tomohiro Watanabe,Kosuke Minaga,Akane Hara,Tomoe Yoshikawa,Ayana Okamoto,Kentaro Yamao,Mamoru Takenaka,Ah-Mee Park,Masatoshi Kudo

    Autoimmune pancreatitis (AIP) is a pancreatic manifestation of a newly proposed disease entity, IgG4-related disease (IgG4-RD), characterized by enhanced IgG4 antibody responses and involvement of multiple organs. We have previously reported that innate immune activation contributes to the development of AIP and IgG4-RD, as these diseases are characterized by the production of IFN-α and IL-33 by plasmacytoid

    更新日期:2019-11-01
  • Requirement for memory B-cell activation in protection from heterologous influenza virus reinfection.
    Int. Immunol. (IF 3.519) Pub Date : 2019-11-08
    Sarah Leach,Ryo Shinnakasu,Yu Adachi,Masatoshi Momota,Chieko Makino-Okamura,Takuya Yamamoto,Ken J Ishii,Hidehiro Fukuyama,Yoshimasa Takahashi,Tomohiro Kurosaki

    While two memory compartments, memory B cells and long-lived plasma cells, are thought to contribute to the successful establishment of memory recall responses, the unique roles of each cellular compartment are still unclear. Herein, by tracing influenza anti-hemagglutinin (HA)-specific antibodies in mice, we demonstrate that pre-existing antibodies secreted by long-lived plasma cells are essential

    更新日期:2019-11-01
  • Discs large homolog 1 regulates B-cell proliferation and antibody production.
    Int. Immunol. (IF 3.519) Pub Date : 2019-11-08
    Xuejiao Dong,Xinxin Li,Ce Liu,Kun Xu,Yi Shi,Wanli Liu

    Antibody production results from B-cell activation and proliferation upon antigen binding. Discs large homolog 1 (Dlg1), a scaffold protein from the membrane-associated guanylate kinase family, has been shown to regulate the antigen receptor signaling and cell polarity in lymphocytes; however, the physiological function of Dlg1 in humoral responses is not completely clear. Here, we addressed this question

    更新日期:2019-11-01
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