International immunology最新文献

The tryptophan metabolic pathway of the microbiome and host cells in health and disease. 微生物组和宿主细胞在健康和疾病中的色氨酸代谢途径。

IF 5.4 4区医学

International immunology Pub Date : 2024-11-14 DOI: 10.1093/intimm/dxae035

Kentaro Miyamoto, Tomohisa Sujino, Takanori Kanai

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

γδ intraepithelial lymphocytes acquire the ability to produce IFN-γ in a different time course than αβ intraepithelial lymphocytes. γδ上皮内淋巴细胞获得产生 IFN-γ 的能力的时间过程与 αβ 上皮内淋巴细胞不同。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-14 DOI: 10.1093/intimm/dxae034

Shizue Tani-Ichi, Koichi Ikuta

{"title":"γδ intraepithelial lymphocytes acquire the ability to produce IFN-γ in a different time course than αβ intraepithelial lymphocytes.","authors":"Shizue Tani-Ichi, Koichi Ikuta","doi":"10.1093/intimm/dxae034","DOIUrl":"10.1093/intimm/dxae034","url":null,"abstract":"An age-dependent increase in interferon (IFN)-γ expression by intestinal intraepithelial lymphocytes (IELs) contributes to the acquisition of resistance to infection by pathogens. However, how IELs acquire the ability to produce IFN-γ remains to be elucidated. Here, we report that IELs in the small intestine acquire the ability to rapidly produce IFN-γ at two distinct life stages. TCRαβ+ IELs (αβIELs) started producing IFN-γ at 4 weeks of age, within 1 week after weaning. In contrast, TCRγδ+ IELs (γδIELs) started producing IFN-γ at 7 weeks of age. In mice lacking Eγ4, an enhancer of the TCRγ locus (Eγ4-/- mice), Thy-1+ Vγ5+ γδIELs, a major subpopulation of γδIELs, were specifically reduced and their ability to produce IFN-γ was severely impaired, whereas Vγ2+ γδIELs normally produced IFN-γ. In Eγ4-/- mice, TCR expression levels were reduced in Vγ5+ γδIEL precursors in the thymus but unchanged in the Vγ5+ IELs. Nevertheless, TCR responsiveness in Vγ5+ γδIELs was impaired in Eγ4-/- mice, suggesting that the TCR signal received in the thymus may determine TCR responsiveness and the ability to produce IFN-γ in the gut. These results suggest that αβIELs and γδIELs start producing IFN-γ at different life stages and that the ability of Vγ5+ γδIELs to produce IFN-γ in the gut may be predetermined by TCR signalling in IEL precursors in the thymus.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"653-661"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247959","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

Synchronized development of thymic eosinophils and thymocytes. 胸腺嗜酸性粒细胞和胸腺细胞的同步发育

IF 5.4 4区医学

International immunology Pub Date : 2024-11-14 DOI: 10.1093/intimm/dxae037

Ayami Ota, Takahiro Iguchi, Sachiko Nitta, Ryunosuke Muro, Nanami Mino, Masayuki Tsukasaki, Josef M Penninger, Takeshi Nitta, Hiroshi Takayanagi

{"title":"Synchronized development of thymic eosinophils and thymocytes.","authors":"Ayami Ota, Takahiro Iguchi, Sachiko Nitta, Ryunosuke Muro, Nanami Mino, Masayuki Tsukasaki, Josef M Penninger, Takeshi Nitta, Hiroshi Takayanagi","doi":"10.1093/intimm/dxae037","DOIUrl":"10.1093/intimm/dxae037","url":null,"abstract":"The thymus is an organ required for T cell development and is also an eosinophil-rich organ; however, the nature and function of thymic eosinophils remain unclear. Here, we characterized the gene expression and differentiation mechanism of thymic eosinophils in mice. Thymic eosinophils showed a distinct gene expression profile compared with other organ-resident eosinophils. The number of thymic eosinophils was controlled by medullary thymic epithelial cells (mTECs). In Rag-deficient mice, the unique gene expression signature of thymic eosinophils was lost but restored by pre-T cell receptor signalling, which induces CD4+ CD8+ thymocyte differentiation, indicating that T cell differentiation beyond the CD4- CD8- stage is necessary and sufficient for the induction of thymic eosinophils. These results demonstrate that thymic eosinophils are quantitatively and qualitatively regulated by mTECs and developing thymocytes, respectively, suggesting that thymic eosinophils are a distinct, thymus-specific cell subset, induced by interactions with thymic cells.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"617-628"},"PeriodicalIF":5.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446094","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

Regulation of memory CD4+ T-cell generation by intrinsic and extrinsic IL-27 signaling during malaria infection. 在疟疾感染过程中，IL-27 的内在和外在信号调节记忆 CD4+ T 细胞的生成。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-14 DOI: 10.1093/intimm/dxae039

Sanjaadorj Tsogtsaikhan, Shin-Ichi Inoue, Ganchimeg Bayarsaikhan, Maria Lourdes Macalinao, Daisuke Kimura, Mana Miyakoda, Masahiro Yamamoto, Hiromitsu Hara, Hiroki Yoshida, Katsuyuki Yui

{"title":"Regulation of memory CD4+ T-cell generation by intrinsic and extrinsic IL-27 signaling during malaria infection.","authors":"Sanjaadorj Tsogtsaikhan, Shin-Ichi Inoue, Ganchimeg Bayarsaikhan, Maria Lourdes Macalinao, Daisuke Kimura, Mana Miyakoda, Masahiro Yamamoto, Hiromitsu Hara, Hiroki Yoshida, Katsuyuki Yui","doi":"10.1093/intimm/dxae039","DOIUrl":"10.1093/intimm/dxae039","url":null,"abstract":"The generation and maintenance of memory T cells are regulated by various factors, including cytokines. Previous studies have shown that IL-27 is produced during the early acute phase of Plasmodium chabaudi chabaudi AS (Pcc) infection and inhibits the development of Th1-type memory CD4+ T cells. However, whether IL-27 acts directly on its receptor on Plasmodium-specific CD4+ T cells or indirectly via its receptor on other immune cells remains unclear. We aimed to determine the role of IL-27 receptor signaling in different immune cell types in regulating the generation and phenotype of memory CD4+ T cells during Plasmodium infection. We utilized Plasmodium-specific T-cell antigen receptor (TCR) transgenic mice, PbT-II, and Il27rα-/- mice to assess the direct and indirect effects of IL-27 signaling on memory CD4+ T-cell generation. Mice were transferred with PbT-II or Il27rα-/- PbT-II cells and infected with Pcc. Conditional knockout mice lacking the IL-27 receptor in T cells or dendritic cells were employed to discern the specific immune cell types involved in IL-27 receptor signaling. High levels of memory in PbT-II cells with Th1-shift occurred only when both PbT-II and host cells lacked the IL-27 receptor, suggesting the predominant inhibitory role of IL-27 signaling in both cell types. Furthermore, IL-27 receptor signaling in T cells limited the number of memory CD4+ T cells, while signaling in both T and dendritic cells contributed to the Th1 dominance of memory CD4+ T cells. These findings underscore the complex cytokine signaling network regulating memory CD4+ T cells during Plasmodium infection.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"629-640"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418843","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 role of polyreactive memory B cells in systemic lupus erythematosus. 多反应记忆 B 细胞在系统性红斑狼疮中的作用。

IF 4.8 4区医学

International immunology Pub Date : 2024-11-08 DOI: 10.1093/intimm/dxae058

Keishi Fujio, Toshiyuki Ushijima, Tomohisa Okamura, Mineto Ota

{"title":"The role of polyreactive memory B cells in systemic lupus erythematosus.","authors":"Keishi Fujio, Toshiyuki Ushijima, Tomohisa Okamura, Mineto Ota","doi":"10.1093/intimm/dxae058","DOIUrl":"https://doi.org/10.1093/intimm/dxae058","url":null,"abstract":"In systemic lupus erythematosus (SLE), the production of autoantibodies is a crucial characteristic, and B cells play a significant role in its pathogenesis. B cells are the immune cells most associated with the genetic predispositions of SLE, and recent clinical studies showing that anti-CD19 CAR-T cell therapy induces drug-free remission have underscored the importance of B cells in SLE. Meanwhile, various B cell subsets exist across different stages of differentiation, from naive B cells to plasma-cells, and identifying the important subpopulations within SLE remains a critical future challenge. Years of B cell repertoire analyses have revealed the importance of polyreactive B cell receptors (BCRs) and autoantibodies that react to a various self-antigens and microbial antigens. Particularly, memory B cells with polyreactive BCRs, which play a crucial role in biological defense during the fetal stage, are characteristically differentiated in SLE. Type I interferon-mediated expression of CXCL13 and IL21 in CD4+ T cells is associated with the development of polyreactive memory B cells. The expansion of the polyreactive B cell repertoire, vital for defending against infections such as viruses, may exert an intrinsic function in SLE.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602068","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 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":" ","pages":"559-566"},"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":" ","pages":"579-584"},"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

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":" ","pages":"585-594"},"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

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":" ","pages":""},"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