International immunology最新文献

Analysis of antigen specificity of Treg cell clonotypes expanded upon SARS-CoV-2 infection.

IF 4.8 4区医学

International immunology Pub Date : 2024-12-12 DOI: 10.1093/intimm/dxae072

Yukiko Takeuchi, Eri Ishikawa, Takashi Sato, Masaharu Shinkai, Yoshimasa Takahashi, Xiuyuan Lu, Sho Yamasaki

{"title":"Analysis of antigen specificity of Treg cell clonotypes expanded upon SARS-CoV-2 infection.","authors":"Yukiko Takeuchi, Eri Ishikawa, Takashi Sato, Masaharu Shinkai, Yoshimasa Takahashi, Xiuyuan Lu, Sho Yamasaki","doi":"10.1093/intimm/dxae072","DOIUrl":"https://doi.org/10.1093/intimm/dxae072","url":null,"abstract":"The pandemic outbreak of SARS-CoV-2 has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses. If SARS-CoV-2-specific Tregs are developed during infection, they may counteract anti-viral immunity and cause severe symptom. To address this possibility, we conducted single-cell TCR-RNA-sequencing of PBMCs from convalescent COVID-19 patients. Among thirteen donors, one with severe symptom had substantially more FOXP3-expressing Treg clonotypes activated in the presence of SARS-CoV-2 virion or other major antigen proteins. To define the reactivity of these Treg clonotypes, fifteen highly expanded Treg clonotypes were reconstituted into reporter cells and stimulated with 27 distinct peptide pools that cover all SARS-CoV-2 proteins. However, none of these clonotypes react to any SARS-CoV-2 antigens. Instead, the reporter cells expressing one TCR clonotype (23599) were activated in the presence of EBV-transformed B cells without adding exogenous antigens. Furthermore, 23599 TCR-expressing cells were activated by non-transformed naïve syngenic B cells in DQA1*03:03-DQB1*04:01-dependent manner, suggesting that clonotype 23599 may be autoreactive. This Treg clonotype, 23599, was also detected in a public TCR database, and significantly expanded in COVID-19 patients compared to healthy donors. These results suggest that SARS-CoV-2 is not the dominant antigen inducing Treg during infection.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-5-producing group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils. 产生 IL-5 的第 2 组先天性淋巴细胞与嗜酸性粒细胞合作，促进不依赖 T 细胞的 IgA 生成。

IF 4.8 4区医学

International immunology Pub Date : 2024-12-04 DOI: 10.1093/intimm/dxae070

Tsutomu Yanagibashi, Masashi Ikutani, Terumi Nagai, Makoto Arita, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu

{"title":"IL-5-producing group 2 innate lymphoid cells promote T cell-independent IgA production in cooperation with eosinophils.","authors":"Tsutomu Yanagibashi, Masashi Ikutani, Terumi Nagai, Makoto Arita, Yasuharu Watanabe, Yoshinori Nagai, Kiyoshi Takatsu","doi":"10.1093/intimm/dxae070","DOIUrl":"https://doi.org/10.1093/intimm/dxae070","url":null,"abstract":"Intestinal bacteria play a critical role in the regulation of the host immune system and an imbalance in intestinal bacterial composition induces various host diseases. Therefore, maintaining a balance in the intestinal bacterial composition is crucial for health. Immunoglobulin A (IgA), produced through T cell-dependent and T cell-independent (TI) pathways, is essential for host defense against pathogen invasion and maintaining the balance of intestinal symbiotic bacteria. Interleukin (IL)-5 is constitutively produced by group 2 innate lymphoid cells (ILC2s) and plays a critical role in the survival and proliferation of B cells and eosinophils. Here, we show that the role of IL-5-producing ILC2s in intestinal TI IgA production at steady state using TCRα deficient mice. In this mouse model, ILC2s increased fecal TI IgA levels in a non-inflammatory state in an IL-5-dependent manner. The administration of recombinant IL-33 (rIL-33) increased the amount of TI IgA production, accompanied by an increase in the number of IL-5-producing ILC2s in the large intestine. In addition, rIL-33 treatment increased IL-5-dependent IgA+ cells in isolated lymphoid follicles, the site of TI IgA production. Furthermore, eosinophils recruited by ILC2s were required for the maximal production of IgA in the TI pathway. Moreover, IL-5 increased the frequency of TI IgA-binding intestinal bacteria and was involved in the maintenance of intestinal bacterial composition. These findings indicate that IL-5-producing ILC2s together with eosinophils contribute to TI IgA production. In addition to their role in TI IgA production, IL-5-producing ILC2s may contribute to the homeostasis of intestinal commensal bacteria.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A complex of NLRP3 with caspase-4 is essential for inflammasome activation by Tannerella forsythia infection.

IF 4.8 4区医学

International immunology Pub Date : 2024-12-03 DOI: 10.1093/intimm/dxae071

Chen Wei Hsu, Tokuju Okano, Yuiko Niinuma, Anongwee Leewananthawet, Tamako Iida, Poramed Onsoi, Kotchakorn Boonyaleka, Hiroshi Ashida, Toshihiko Suzuki

{"title":"A complex of NLRP3 with caspase-4 is essential for inflammasome activation by Tannerella forsythia infection.","authors":"Chen Wei Hsu, Tokuju Okano, Yuiko Niinuma, Anongwee Leewananthawet, Tamako Iida, Poramed Onsoi, Kotchakorn Boonyaleka, Hiroshi Ashida, Toshihiko Suzuki","doi":"10.1093/intimm/dxae071","DOIUrl":"https://doi.org/10.1093/intimm/dxae071","url":null,"abstract":"Periodontitis, a chronic inflammatory disease of periodontal tissue, is often associated with a group of pathogenic bacteria known as the \"red complex,\" including Tannerella forsythia (T. forsythia). Previous papers showed that T. forsythia induces many kinds of inflammatory cytokines including IL-1β regulated by inflammasome activation. However, the physiological function for periodontitis and mechanism to induce inflammasome activation by T. forsythia infection are poorly understood. In this study, we demonstrate that NLRP3 and caspase-4 are essential for inflammasome activation by T. forsythia infection, playing a crucial role in IL-1β maturation in THP-1 cells. We also showed that knockout of ASC or GSDMD suppress the pyroptotic cell death. Moreover, co-immunoprecipitation assays confirmed the formation of a complex involving caspase-4, NLRP3, and ASC following T. forsythia infection. Additionally, reactive oxygen species (ROS) production was identified as a key factor in caspase-4-mediated NLRP3 inflammasome activation by T. forsythia infection. These results enhance our understanding of inflammasome activation in response to T. forsythia infection and provide new insights into the pathogenic mechanisms of periodontitis.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The immune memory of innate immune systems. 先天性免疫系统的免疫记忆。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-26 DOI: 10.1093/intimm/dxae067

Yasuhiro Kato, Atsushi Kumanogoh

引用次数: 0

CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection. 依赖 CCR2 的炎性单核细胞胎盘迁移可抑制弓形虫感染引起的异常妊娠。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-25 DOI: 10.1093/intimm/dxae046

Naganori Kamiyama, Mai Ueno, Yuma Sasaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yasuhiro Soga, Yomei Kagoshima, Supanuch Ekronarongchai, Masaaki Okamoto, Masahiro Yamamoto, Takashi Kobayashi

{"title":"CCR2-dependent placental migration of inflammatory monocytes suppresses abnormal pregnancies caused by Toxoplasma gondii infection.","authors":"Naganori Kamiyama, Mai Ueno, Yuma Sasaki, Thanyakorn Chalalai, Nozomi Sachi, Sotaro Ozaka, Yasuhiro Soga, Yomei Kagoshima, Supanuch Ekronarongchai, Masaaki Okamoto, Masahiro Yamamoto, Takashi Kobayashi","doi":"10.1093/intimm/dxae046","DOIUrl":"10.1093/intimm/dxae046","url":null,"abstract":"Toxoplasma gondii (T. gondii) is a zoonotic protozoan parasite that causes congenital toxoplasmosis, including fetal death, abortion, stillbirth, morphological abnormalities, and premature birth. Primary T. gondii infection in pregnant women results in congenital toxoplasmosis. C-C chemokine receptor (CCR) 2 is reportedly a critical host defense factor against T. gondii infection. However, details of the role of CCR2 in the host immune response to T. gondii in congenital toxoplasmosis remain unclear. Here, we infected pregnant CCR2-deficient mice with T. gondii, resulting in stillbirth, embryonic resorption, fetal morphological abnormalities, and preterm delivery at significantly higher rates than those in pregnant wild-type (WT) mice. Consistent with the severity of abnormal pregnancy, a large area of placental hemorrhage and a large number of T. gondii infections around the hemorrhagic area were observed in the placentas of CCR2-deficient mice. In addition, the accumulation of inflammatory monocytes in the placenta was reduced in CCR2-deficient mice during infection. We further confirmed that the adoptive transfer of inflammatory monocytes collected from WT mice into T. gondii-infected pregnant CCR2-deficient mice effectively suppressed placental damage and abnormal pregnancy. Collectively, CCR2 contributes to pregnancy maintenance by regulating the migration of inflammatory monocytes into the placenta of T. gondii-infected pregnant mice.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"39-52"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis. 在小鼠结肠炎中，典型 Hippo 通路成分可调节固有膜调节性 T 细胞和 T 辅助 17 样调节性 T 细胞的分化。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-25 DOI: 10.1093/intimm/dxae043

Liuqing Ge, Min Xu, Meifang Huang, Shaoping Liu, Zhidai Zhou, Ziqin Xia, Shouquan Dong, Qiu Zhao, Ruiping Zhu, Feng Zhou

{"title":"The canonical Hippo pathway components modulate the differentiation of lamina propria regulatory T cells and T helper 17-like regulatory T cells in mouse colitis.","authors":"Liuqing Ge, Min Xu, Meifang Huang, Shaoping Liu, Zhidai Zhou, Ziqin Xia, Shouquan Dong, Qiu Zhao, Ruiping Zhu, Feng Zhou","doi":"10.1093/intimm/dxae043","DOIUrl":"10.1093/intimm/dxae043","url":null,"abstract":"Regulatory T cells (Tregs) ameliorate inflammatory bowel diseases. However, their plasticity is not completely understood. In this study using a mouse colitis model, Tregs and T helper 17 (Th17)-like Tregs were detected and sorted using flow cytometry, followed by transcriptome sequencing, real-time reverse transcription polymerase chain reaction, and flow cytometry to analyze the mRNA profiles of these cells. Treg plasticity was evaluated by in vitro differentiation assays. The immunosuppressive activities of Tregs and Th17-like Tregs were assessed in an adoptive transfer assay. We found Treg-derived Th17-like Tregs in inflamed colonic lamina propria (LP). LP Th17-like Tregs expressed higher Th17-related cytokines and lower immunosuppressive cytokines compared with LP Tregs. Notably, Tregs expressed higher Yes-associated protein 1 (YAP1) but lower transcriptional coactivator with PDZ-binding motif (TAZ) than Th17-like Tregs. Verteporfin-mediated inhibition of YAP1 activity enhanced Th17-like Treg generation, whereas IBS008739-induced TAZ activation did not affect Th17-like Treg generation. Besides, verteporfin enhanced while IBS008739 suppressed the differentiation of Th17-like Tregs into Th17 cells. Furthermore, YAP1 activated STAT5 signaling in Tregs, whereas YAP1 and TAZ activated STAT3 and STAT5 signaling in Th17-like Tregs. Compared with Tregs, Th17-like Tregs were less efficacious in ameliorating colitis. Therefore, YAP1 suppressed Treg differentiation into Th17-like Tregs. Both YAP1 and TAZ inhibited the differentiation of Th17-like Tregs into Th17 cells. Therefore, YAP1 and TAZ probably maintain the immunosuppressive activities of Tregs and Th17-like Tregs in colitis.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"25-38"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation. 维生素 D 的活性形式（钙三醇）可在滤泡辅助性 T 细胞分化过程中促进 CXCR5 的表达。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-25 DOI: 10.1093/intimm/dxae045

Makoto Iwata, Ayumi Takada, Rei Sakamoto, Si-Young Song, Etsuro Ito

{"title":"The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation.","authors":"Makoto Iwata, Ayumi Takada, Rei Sakamoto, Si-Young Song, Etsuro Ito","doi":"10.1093/intimm/dxae045","DOIUrl":"10.1093/intimm/dxae045","url":null,"abstract":"Follicular helper T (Tfh) cells promote B cell differentiation and antibody production in the B cell follicles of secondary lymphoid organs. Tfh cells express their signature transcription factor BCL6, interleukin (IL)-21, and surface molecules including inducible T cell costimulator (ICOS), programmed cell death-1 (PD-1), and C-X-C motif chemokine receptor 5 (CXCR5). Migration of Tfh cells to B cell follicles largely depends on the CXCR5 expression induced by interactions with antigen-presenting dendritic cells in the T cell area. How Tfh cells acquire sufficient levels of CXCR5 expression, however, has remained unclear. Using our in vitro culture system to generate CXCR5low Tfh-like cells from naive CD4+ T cells with IL-6 in the absence of other cell types, we found that the active form of vitamin D, calcitriol, markedly enhanced CXCR5 expression after the release from persistent T cell receptor (TCR) stimulation. CH-223191, an aryl hydrocarbon receptor antagonist, further enhanced CXCR5 expression. IL-12 but not IL-4, in place of IL-6, also supported calcitriol to enhance CXCR5 expression even before the release from TCR stimulation, whereas the cell viability sharply decreased after the release. The Tfh-like cells generated with IL-6 and calcitriol exhibited chemotaxis toward C-X-C motif chemokine ligand 13 (CXCL13), expressed IL-21, and helped B cells to produce IgG antibodies in vitro more efficiently than Tfh-like cells generated without added calcitriol. Calcitriol injections into antigen-primed mice increased the proportion of CXCR5+PD-1+CD4+ cells in their lymphoid organs, and enhanced T cell entry into B cell follicles. These results suggest that calcitriol promotes CXCR5 expression in developing Tfh cells and regulates their functional differentiation.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"53-70"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells. 控制慢性炎症性疾病的新方法，重点关注免疫细胞的内溶酶体系统。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-25 DOI: 10.1093/intimm/dxae041

Noriko Toyama-Sorimachi

{"title":"New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells.","authors":"Noriko Toyama-Sorimachi","doi":"10.1093/intimm/dxae041","DOIUrl":"10.1093/intimm/dxae041","url":null,"abstract":"Chronic inflammation is implicated in many types of diseases, including cardiovascular, neurodegenerative, metabolic, and immune disorders. The search for therapeutic targets to control chronic inflammation often involves narrowing down the various molecules associated with pathology that have been discovered by various omics analyses. Herein, a different approach to identify therapeutic targets against chronic inflammation is proposed and one such target is discussed as an example. In chronically inflamed tissues, a large number of cells receive diverse proinflammatory signals, the intracellular signals are intricately integrated, and complicated intercellular interactions are orchestrated. This review focuses on effectively blocking this chaotic inflammatory signaling network via the endolysosomal system, which acts as a cellular signaling hub. In endolysosomes, the inflammatory signals mediated by pathogen sensors, such as Toll-like receptors, and the signals from nutrient and metabolic pathways are integrally regulated. Disruption of endolysosome signaling results in a strong anti-inflammatory effect by disrupting various signaling pathways, including pathogen sensor-mediated signals, in multiple immune cells. The endolysosome-resident amino acid transporter, solute carrier family 15 member 4 (SLC15A4), which plays an important role in the regulation of endolysosome-mediated signals, is a promising therapeutic target for several inflammatory diseases, including autoimmune diseases. The mechanisms by which SLC15A4 regulates inflammatory responses may provide a proof of concept for the efficacy of therapeutic strategies targeting immune cell endolysosomes.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"15-24"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease. 树突状细胞和调节性 T 细胞串联在控制健康和疾病方面的多种作用。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-25 DOI: 10.1093/intimm/dxae042

Sayuri Yamazaki

{"title":"Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease.","authors":"Sayuri Yamazaki","doi":"10.1093/intimm/dxae042","DOIUrl":"10.1093/intimm/dxae042","url":null,"abstract":"Dendritic cells (DCs) are specialized antigen-presenting cells for lymphocytes, including regulatory T (Treg) cells, a subset of CD4+ T cells expressing CD25 and Foxp3, a transcription factor. Treg cells maintain immunological self-tolerance in mice and humans, and suppress autoimmunity and other various immune responses such as tumor immunity, transplant rejection, allergy, responses to microbes, and inflammation. Treg-cell proliferation is controlled by antigen-presenting DCs. On the other hand, Treg cells suppress the function of DCs by restraining DC maturation. Therefore, the interaction between DCs and Treg cells, DC-Treg crosstalk, could contribute to controlling health and disease. We recently found that unique DC-Treg crosstalk plays a role in several conditions. First, Treg cells are expanded in ultraviolet B (UVB)-exposed skin by interacting with DCs, and the UVB-expanded Treg cells have a healing function. Second, manipulating DC-Treg crosstalk can induce effective acquired immune responses against severe acute respiratory syndrome coronavirus 2 antigens without adjuvants. Third, Treg cells with a special feature interact with DCs in the tumor microenvironment of human head and neck cancer, which may contribute to the prognosis. Understanding the underlying mechanisms of DC-Treg crosstalk may provide a novel strategy to control health and disease.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"5-14"},"PeriodicalIF":4.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Supersulphides suppress type-I and type-II interferon responses by blocking JAK/STAT signalling in macrophages. 超硫化物通过阻断巨噬细胞中的 JAK/STAT 信号传导抑制Ⅰ型和Ⅱ型干扰素反应

IF 4.8 4区医学

International immunology Pub Date : 2024-11-14 DOI: 10.1093/intimm/dxae040

Xiaoyan Li, Touya Toyomoto, Tianli Zhang, Chunyu Guo, Stephen Lindahl, Hiroyasu Tsutsuki, Ming Xian, Tomohiro Sawa

{"title":"Supersulphides suppress type-I and type-II interferon responses by blocking JAK/STAT signalling in macrophages.","authors":"Xiaoyan Li, Touya Toyomoto, Tianli Zhang, Chunyu Guo, Stephen Lindahl, Hiroyasu Tsutsuki, Ming Xian, Tomohiro Sawa","doi":"10.1093/intimm/dxae040","DOIUrl":"10.1093/intimm/dxae040","url":null,"abstract":"Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumour cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumour effects. The main subclasses of IFNs include type-I (e.g. IFN-α and IFN-β) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulphide donors, which have polysulphide structures in which three or more sulphur atoms are linked within the molecules, IFN-β-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulphides and the mechanism of this suppression are unknown. This study demonstrated that supersulphide donor N-acetyl-L-cysteine tetrasulphide (NAC-S2) can inhibit IFN signalling in macrophages stimulated not only with IFN-α/β but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributing to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, the hydrogen sulphide (H2S) donor NaHS failed to inhibit IFN signalling. Similar to NAC-S2, the carbohydrate-based supersulphide donor thioglucose tetrasulphide (TGS4) was capable of strongly inhibiting tumour necrosis factor-α production, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of the molecular mechanisms by which supersulphide donors exhibit their inhibitory actions towards JAK/STAT signalling is a necessary basis for the development of supersulphide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signalling.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"641-652"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0