International immunology最新文献

The role of dendritic cells in the instruction of helper T cells in the allergic march. 树突状细胞在过敏前行过程中对辅助性 T 细胞的指导作用。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae050

Masato Kubo, Yasuyo Harada, Takanori Sasaki

{"title":"The role of dendritic cells in the instruction of helper T cells in the allergic march.","authors":"Masato Kubo, Yasuyo Harada, Takanori Sasaki","doi":"10.1093/intimm/dxae050","DOIUrl":"10.1093/intimm/dxae050","url":null,"abstract":"Allergy is a complex array of diseases influenced by innate and adaptive immunity, genetic polymorphisms, and environmental triggers. Atopic dermatitis is a chronic inflammatory skin disease characterized by barrier defects and immune dysregulation, sometimes leading to asthma and food allergies because of the atopic march. During atopic skin inflammation, Langerhans cells and dendritic cells (DCs) in the skin capture and deliver allergen information to local lymph nodes. DCs are essential immune sensors coordinating immune reactions by capturing and presenting antigens to T cells. In the context of allergic responses, DCs play a crucial role in instructing two types of helper T cells-type 2 helper T (Th2) cells and follicular helper T (TFH) cells-in allergic responses and IgE antibody responses. In skin sensitization, the differentiation and function of Th2 cells and TFH cells are influenced by skin-derived factors, including epithelial cytokines, chemokines, and signalling pathways to modify the function of migratory DCs and conventional DCs. In this review, we aim to understand the specific mechanisms involving DCs in allergic responses to provide insights into the pathogenesis of allergic diseases and potential therapeutic strategies.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004175","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 skin barrier and microbiome in infantile atopic dermatitis development: can skincare prevent onset? 婴儿特应性皮炎发育过程中的皮肤屏障和微生物群：皮肤护理能预防发病吗？

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae038

Tomoka Ito, Yuumi Nakamura

{"title":"The skin barrier and microbiome in infantile atopic dermatitis development: can skincare prevent onset?","authors":"Tomoka Ito, Yuumi Nakamura","doi":"10.1093/intimm/dxae038","DOIUrl":"10.1093/intimm/dxae038","url":null,"abstract":"Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies, and practices in allergy prevention.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418844","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

Ro5-4864, a translocator protein ligand, regulates T cell-mediated inflammatory responses in skin. 转运蛋白配体 Ro5-4864 可调节 T 细胞介导的皮肤炎症反应。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae065

Yuka Sendai, Kazuyoshi Takeda, Keisuke Ohta, Susumu Nakae, Kyotaro Koshika, Kei Kitamura, Makoto Higuchi, Tatsuya Ichinohe, Toshifumi Azuma, Ko Okumura, Tatsukuni Ohno

{"title":"Ro5-4864, a translocator protein ligand, regulates T cell-mediated inflammatory responses in skin.","authors":"Yuka Sendai, Kazuyoshi Takeda, Keisuke Ohta, Susumu Nakae, Kyotaro Koshika, Kei Kitamura, Makoto Higuchi, Tatsuya Ichinohe, Toshifumi Azuma, Ko Okumura, Tatsukuni Ohno","doi":"10.1093/intimm/dxae065","DOIUrl":"https://doi.org/10.1093/intimm/dxae065","url":null,"abstract":"Translocator protein (TSPO) is a mitochondrial outer membrane protein expressed on a variety of immune cells, including macrophages, dendritic cells, and T cells, in addition to neurons and steroid-producing cells. Previous studies of TSPO ligands have suggested that TSPO is involved in multiple cellular functions, including steroidogenesis, immunomodulation, and cell proliferation. Currently, there are limited reports on the effects of TSPO or TSPO ligands on T cell-mediated immune responses. We here investigated the involvement of TSPO/TSPO ligand in T cell responses using a 2,4-dinitro-1-fluorobenzene (DNFB)-induced contact hypersensitivity (CH) model. Treatment with Ro5-4864, a TSPO ligand, during DNFB sensitization reduced the number and activation status of CD4+ and CD8+ T cells in draining lymph nodes and alleviated skin inflammation after DNFB challenge. Adoptive transfer of Ro5-4864-treated mouse-derived DNFB-sensitized T cells to naïve mice inhibited CH responses after DNFB challenge. Ro5-4864-treated sensitized T cells showed lower proliferative responses when stimulated with DNFB-pulsed antigen-presenting cells compared to control-treated sensitized T cells. Ro5-4864 also suppressed cell proliferation, as well as adenosine triphosphate and lactate production, during T cell activation. Moreover, the inhibitory effects of Ro5-4864 on T cell responses were conserved in TSPO-deficient cells. Our results suggest that Ro5-4864 inhibits CH responses by suppressing energy metabolism, at least via glycolysis, to reduce the T cell primary response in a TSPO-independent manner.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499829","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

Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death. 1 型和 2 型免疫细胞的功能失调：从枯竭样 ILC2 及其活化诱导的细胞死亡中汲取教训。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae032

Takashi Ebihara, Toshiki Yamada, Akane Fuchimukai, Shunsuke Takasuga, Tentaro Endo, Takechiyo Yamada, Megumi Tatematsu

{"title":"Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.","authors":"Takashi Ebihara, Toshiki Yamada, Akane Fuchimukai, Shunsuke Takasuga, Tentaro Endo, Takechiyo Yamada, Megumi Tatematsu","doi":"10.1093/intimm/dxae032","DOIUrl":"10.1093/intimm/dxae032","url":null,"abstract":"The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses, especially by CD8 T-cells against tumors or virus-infected cells, and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit dysfunctional phenotypes in tumor microenvironments and in chronic viral infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy. In mouse models of chronic parasitic worm infections, Th2 cells display impaired type 2 immune responses. Chronic airway allergy induces exhausted-like ILC2s that quickly fall into activation-induced cell death to suppress exaggerated inflammation. Thus, the modes of exhaustion/dysfunction are quite diverse and rely on the types of inflammation and the cells. In this review, we summarize current knowledge of lymphocyte exhaustion/dysfunction in the context of type 1 and type 2 immune responses and discuss ILC2-specific regulatory mechanisms during chronic allergy.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093264","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

JunB is required for CD8+ T cell responses to acute infections. CD8+ T 细胞对急性感染的反应需要 JunB。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-19 DOI: 10.1093/intimm/dxae063

Shukla Sarkar, Naoyuki Taira, Tsung-Han Hsieh, Hsiao-Chiao Chien, Masato Hirota, Shin-Ichi Koizumi, Daiki Sasaki, Miho Tamai, Yu Seto, Mio Miyagi, Hiroki Ishikawa

{"title":"JunB is required for CD8+ T cell responses to acute infections.","authors":"Shukla Sarkar, Naoyuki Taira, Tsung-Han Hsieh, Hsiao-Chiao Chien, Masato Hirota, Shin-Ichi Koizumi, Daiki Sasaki, Miho Tamai, Yu Seto, Mio Miyagi, Hiroki Ishikawa","doi":"10.1093/intimm/dxae063","DOIUrl":"https://doi.org/10.1093/intimm/dxae063","url":null,"abstract":"Basic-leucine zipper transcription factor ATF-like (BATF) and interferon regulatory factor 4 (IRF4) are crucial transcription factors for generation of cytotoxic effector and memory CD8+ T cells. JunB is required for expression of genes controlled by BATF and IRF4 in CD4+ T cell responses, but the role of JunB in CD8+ T cells remains unknown. Here, we demonstrate that JunB is essential for cytotoxic CD8+ T cell responses. JunB expression is transiently induced, depending on T cell receptor (TCR) signal strength. JunB deficiency severely impairs clonal expansion of effector CD8+ T cells in response to acute infection with Listeria monocytogenes. Junb-deficient CD8+ T cells fail to control transcription and chromatin accessibility of a specific set of genes regulated by BATF and IRF4, resulting in impaired cell survival, glycolysis, and cytotoxic CD8+ T cell differentiation. Furthermore, JunB deficiency enhances expression of coinhibitory receptors, including programmed death receptor 1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM3) upon activation of naïve CD8+ T cells. These results indicate that JunB, in collaboration with BATF and IRF4, promotes multiple key events in the early stage of cytotoxic CD8+ T cell responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464488","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

Eosinophil and B cell dynamics in the milky spots from Schistosoma mansoni-infected mice - Comparison with spleen and bone marrow, and extramedullary eosinopoiesis. 曼氏血吸虫感染小鼠乳斑中的嗜酸性粒细胞和 B 细胞动态--与脾脏和骨髓以及髓外嗜酸性粒细胞生成的比较。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-18 DOI: 10.1093/intimm/dxae064

Bruno Marques Vieira, Beatriz Fernandes Almeida, Marcelo Pelajo Machado

{"title":"Eosinophil and B cell dynamics in the milky spots from Schistosoma mansoni-infected mice - Comparison with spleen and bone marrow, and extramedullary eosinopoiesis.","authors":"Bruno Marques Vieira, Beatriz Fernandes Almeida, Marcelo Pelajo Machado","doi":"10.1093/intimm/dxae064","DOIUrl":"https://doi.org/10.1093/intimm/dxae064","url":null,"abstract":"The milky spots are structures found in the omentum of humans and other vertebrates, representing a fraction of the lymphomyeloid tissue associated with the celom. They majorly consist of B lymphocytes, T lymphocytes, and macrophages. Also found in smaller quantities are mesothelial, stromal, dendritic, and rare mast cells. In an experimental model of Schistosoma mansoni infection, there is significant activation of the omentum and milky spots, which exhibit numerous eosinophils. Despite being described for many years, the complete profile of cells found in milky spots and their functions remains largely unexplored. Here, we evaluate the leukocyte populations of the milky spots in homeostasis and a murine model of Schistosoma mansoni infection. The histopathological characterizations, phenotypic profile analysis, and characterization of the eosinophilic potential of progenitors and precursors comparing the milky spots with the spleen and bone marrow showed significant activation of milky spots in infected mice, with changes in the profile over the analyzed times, showing signs of migration and activation of eosinophils, with local eosinopoiesis and maintenance of the eosinophilic population. In naive mice, B1a and B1b cells comprise only a small fraction of B lymphocytes. However, B1b cells expand significantly during infection, peaking at 60 DPI before stabilizing by 90 DPI. B1a cells also increase initially but decrease over time. The behavior of milky spots differs from other primary and secondary lymphoid organs, acting as a central lymphoid organ in cavity immunity.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464487","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

PP2A negatively regulates NK cell T-bet expression and anti-tumor effector function. PP2A 负向调节 NK 细胞 T-bet 的表达和抗肿瘤效应功能。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-15 DOI: 10.1093/intimm/dxae057

Yui Shinzawa, Daisuke Hara, Yuki Shinguryo, Satoru Yokoyama, Manabu Kawada, Yoshihiro Hayakawa

{"title":"PP2A negatively regulates NK cell T-bet expression and anti-tumor effector function.","authors":"Yui Shinzawa, Daisuke Hara, Yuki Shinguryo, Satoru Yokoyama, Manabu Kawada, Yoshihiro Hayakawa","doi":"10.1093/intimm/dxae057","DOIUrl":"https://doi.org/10.1093/intimm/dxae057","url":null,"abstract":"The transcription factor T-bet is essential for the anti-tumor effector function of NK cells, but the mechanism regulating its expression in NK cells remains unclear. In this study, we aimed to identify an NK cell intrinsic regulator that controls T-bet expression. Using T-bet-luciferase reporter assay screening, we identified a protein phosphatase inhibitor as a potential activator of T-bet expression. A series of PP2A-specific inhibitors (PP2Ai) or PP2A siRNA induced the expression of T-bet. In PP2Ai-treated mice, the expressions of T-bet and its downstream effector molecules, granzyme B and IFN-γ, were also upregulated in NK cells. Mechanistically, PP2Ai increased the phosphorylation of mTOR and ribosomal protein S6 in NK cells, and mTOR inhibitor canceled the effects of PP2Ai in NK cells. Importantly, NK cells isolated from PP2Ai-treated mice showed higher cytotoxicity and IFN-γ production; therefore, they increased the anti-tumor effector function of NK cells. Accordingly, PP2Ai treatment inhibited lung metastasis of B16 melanoma by NK cell- and mTOR-dependent mechanisms. These results suggest that PP2A negatively regulates NK cell T-bet expression and effector function by an mTOR-dependent mechanism.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464489","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

Intra-tumoral delivery of 5'ppp-dsRNA induces robust anti-tumor response via RIG-I activation and Bcl-2 gene downregulation in murine model of prostate cancer. 在小鼠前列腺癌模型中，5'ppp-dsRNA 的瘤内给药通过 RIG-I 激活和 Bcl-2 基因下调诱导强有力的抗肿瘤反应。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-10 DOI: 10.1093/intimm/dxae061

Kasturi Ganguly, Siddhanath M Metkari, Barnali Biswas, Rambhadur Subedi, Taruna Madan

{"title":"Intra-tumoral delivery of 5'ppp-dsRNA induces robust anti-tumor response via RIG-I activation and Bcl-2 gene downregulation in murine model of prostate cancer.","authors":"Kasturi Ganguly, Siddhanath M Metkari, Barnali Biswas, Rambhadur Subedi, Taruna Madan","doi":"10.1093/intimm/dxae061","DOIUrl":"https://doi.org/10.1093/intimm/dxae061","url":null,"abstract":"Onco-immunotherapy via blocking checkpoint-inhibitors has revolutionized the treatment-landscape of several malignancies, though not in the metastatic castration-resistant prostate cancer (PCa) owing to immunosuppressive and poorly immunogenic \"cold\" tumor microenvironment (TME). Turning up the heat of such cold TME via triggering innate immunity is now of increasing interest to restore immune-surveillance. Retinoic acid-inducible gene- I (RIG-I)-like receptors (RLRs) are cytosolic innate-sensors that can detect exogenous RNAs and induce type-I interferons and other pro-inflammatory signaling. RIG-I activation is suggested to be a valuable addition to the treatment approaches for several cancers. However, the knowledge about RIG-I signaling in PCa remains elusive. The present study evaluated the expression of two important RLRs, RIG-I and melanoma differentiation-associated protein 5 (MDA5) along with their downstream partners, mitochondrial antiviral-signaling protein (MAVS) and ERA G-protein-like 1 (ERAL1) during PCa progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The early stage of PCa revealed a significant increment in the expression of RLRs, but not MAVS. However, the advanced stage showed downregulated RLR signaling. Further, the therapeutic implication of 5'ppp-dsRNA, a synthetic RIG-I agonist and Bcl2 gene silencer has been investigated in vitro and in vivo. Intra-tumoral delivery of 5'ppp-dsRNA regressed tumor growth via triggering tumor cells apoptosis, immunomodulation, and inducing phagocytic \"eat me\" signals. These findings highlight that, for the first time, RIG-I activation and Bcl-2 silencing with 5'ppp-dsRNA can serve as a potent tumor-suppressor strategy in PCa and has a significant clinical implication in transforming \"cold\" TME into immunogenic \"hot\" TME of PCa.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390363","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

An abnormal increase in CD26(-)CD28(-) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus. 系统性红斑狼疮患者 CD26（-）CD28（-）细胞毒性效应 CD4 和 CD8 T 细胞群异常增加。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-09 DOI: 10.1093/intimm/dxae062

Ryo Hatano, Hayato Nakamura, Ayako Yamamoto, Haruna Otsuka, Takumi Itoh, Nao Hosokawa, Jinghui Yu, Sedigheh Ranjbar, Yuta Hasegawa, Tsutomu Sato, Nam H Dang, Kei Ohnuma, Shinji Morimoto, Iwao Sekigawa, Tomonori Ishii, Chikao Morimoto

{"title":"An abnormal increase in CD26(-)CD28(-) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus.","authors":"Ryo Hatano, Hayato Nakamura, Ayako Yamamoto, Haruna Otsuka, Takumi Itoh, Nao Hosokawa, Jinghui Yu, Sedigheh Ranjbar, Yuta Hasegawa, Tsutomu Sato, Nam H Dang, Kei Ohnuma, Shinji Morimoto, Iwao Sekigawa, Tomonori Ishii, Chikao Morimoto","doi":"10.1093/intimm/dxae062","DOIUrl":"https://doi.org/10.1093/intimm/dxae062","url":null,"abstract":"CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in CD26(-) T cell population reflects the abnormal expansion of CD26(-)CD28(-) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single cell RNA sequencing analysis of the CD26(-)CD28(-) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(-)CD28(-) T cells is increased in some active stage SLE patients with renal manifestation. Meanwhile, effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390362","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

Senescence-Associated T cells in Immunosenescence and Diseases. 免疫衰老和疾病中的衰老相关 T 细胞。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-25 DOI: 10.1093/intimm/dxae056

Yuji Fukushima, Ryuji Ueno, Nagahiro Minato, Masakazu Hattori

{"title":"Senescence-Associated T cells in Immunosenescence and Diseases.","authors":"Yuji Fukushima, Ryuji Ueno, Nagahiro Minato, Masakazu Hattori","doi":"10.1093/intimm/dxae056","DOIUrl":"https://doi.org/10.1093/intimm/dxae056","url":null,"abstract":"Age-related changes in the immune system, referred to as immunosenescence, appear to evolve with rather paradoxical manifestations, a diminished adaptive immune capacity, and an increased propensity for chronic inflammation often with autoimmunity, which may underlie the development of diverse disorders with age. Immunosenescent phenotypes are associated with the emergence of unique lymphocyte subpopulations of both T and B lineages. We report that a CD153+ PD-1+ CD4+ T-cell subpopulation with severely attenuated T-cell receptor (TCR)-responsiveness, termed senescence-associated T (SAT) cells, co-evolve with potentially autoreactive CD30+ B cells, such as spontaneous germinal center B cells and age-associated B cells, in aging mice. SAT cells and CD30+ B cells are reciprocally activated with the aid of the interaction of CD153 with CD30 in trans and with the TCR complex in cis, resulting in the restoration of TCR-mediated proliferation and secretion of abundant proinflammatory cytokines in SAT cells and the activation and production of autoantibodies by CD30+ B cells. Besides normal aging, the development of SAT cells coupled with counterpart B cells may be robustly accelerated and accumulated in the relevant tissues of lymphoid or extra-lymphoid organs under chronic inflammatory conditions including autoimmunity and may contribute to the pathogenesis and aggravation of the disorders. This review summarizes and discusses recent advances in the understanding of SAT cells in the contexts of immunosenescent phenotypes, autoimmune and chronic inflammatory diseases and provides a novel therapeutic clue.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346132","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