Mitsuyama H., Iizasa E., Kukita A., Toda S., Yoshida H., Inoue H., Hara H. . Deletion of Card9 eliminates the detrimental facets of mycobacterial adjuvants . Heliyon10 (2024 · 記述言語： 日本語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Heliyon Although mycobacterial adjuvants are capable of eliciting a strong adaptive humoral and cellular immunity, they also sometimes provoke detrimental outcomes, including autoimmune/inflammatory syndromes. Here, we show that the deletion of caspase recruitment domain family member 9 (Card9), a signaling adaptor of a set of innate immune receptors, can eliminate the detrimental effects of mycobacterial adjuvants. Long-lasting tissue-destructive skin inflammation at the site of complete Freund's adjuvant (CFA) injection, lung granuloma formation induced by intratracheal Mycobacterium bovis Bacillus Calmette-Guérin infection, and the incidence and severity of experimental autoimmune encephalomyelitis and collagen-induced arthritis induced by autoantigen immunization with CFA were considerably attenuated in Card9-deficient (Card9−/−) mice compared to control wild-type mice. Card9−/− mice showed impaired development of Th17, but not Th1, in the early phase after autoimmune induction, due to the impaired development of IL-6-producing Sirpαhigh dendritic cells, which are essential for priming pathigenic Th17, in the draining lymph nodes. However, Card9 deletion did not affect overall adaptive antibody production or delayed-type hypersensitivity following immunization with CFA, indicating that humoral and type 1 immune responses remained intact. These results suggest that avoiding the activation of Card9 signaling during vaccination with mycobacteria-containing vaccines may mitigate the risk of detrimental type 3 immune responses, while preserving type 1 immune responses that are effective against intracellular pathogens and cancers. DOI： 10.1016/j.heliyon.2024.e38139 Scopus PubMed
坂田 大治, 野元 裕輔, 山本 雅裕, 中嶋 千紗, 椛島 健治, 吉田 裕樹, 金蔵 拓郎, 原 博満 . IL-27による痒み感覚の抑制 . 日本薬理学会年会要旨集97 ( 0 ) 3-B-O09-3 2023年 詳細を見る 記述言語： 日本語 出版者・発行元： 公益社団法2023 · 記述言語： 日本語 出版者・発行元： 公益社団法人 日本薬理学会 <p>Physiological itch is crucial for host defense because scratching behavior leads to removing potentially harmful organism from the skin. However, itch in chronic disease such as atopic dermatitis induces unpleasant effects. Recent studies have paid attention to type2 cytokines including IL-4, IL-13 and IL-31 as allergic dermatitis-associated itch mediators. Indeed, receptors of these cytokines are expressed on dorsal root ganglion neurons and the cytokines can activate and/or sensitize the neurons directly. However, immune regulation of itch sensation has not yet been fully understood.</p><p>IL-27 is an immunoregulatory cytokine which belongs to IL-12 cytokine family. IL-27 is mainly produced by antigen-presenting cells and transmits the signals via a heterodimeric receptor composed of IL-27 receptor a chain (WSX-1) and gp130. Although IL-27 suppresses Th2 and ILC2 responses, the role of IL-27 in neural system remains to be elucidated.</p><p>Here, we found that mice deficient in WSX-1 showed enhanced scratching behavior against several pruritogens. Conversely, administration of recombinant IL-27 suppressed pruritogen-induced scratching behavior in WT mice. This suppressive effect of IL-27 in itch sensation is abolished in Nav1.8-Cre WSX-1<sup>flox/flox</sup> mice which lack sensory neuron specific WSX-1 expression. In addition, treatment with JAK kinase inhibitor abrogates the effect of IL-27 in scratching behavior. These results imply that IL-27 acts on sensory neuron and suppresses neuronal activity by JAK kinase-dependent manner, leading to regulatory function in itch sensation.</p> DOI： 10.1254/jpssuppl.97.0_3-b-o09-3 CiNii Research
