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論文
- タイトル
- タイトル（英）
- The thyroid hormone receptor beta (TR-β) signaling controls pathogenic Th17 cells in autoimmune disease.
- 参照URL
- https://researchmap.jp/kimura_vision/published_papers/52835675
- 著者
- 著者（英）
- Yoshimitsu Doi,Ben J E Raveney,Atsuko Kimura,Manu S Mallahalli,Kimitoshi Kimura,Wakiro Sato,Shinji Oki,Takashi Yamamura
- 担当区分
- 概要
- 概要（英）
- The role of the thyroid hormone receptor beta (TR-β) in the immune system remains poorly understood; although its effect on TGF-β signaling has been reported in nonimmune systems. Here, we report that Thrb is highly expressed in pathogenic CD4+ T cells that infiltrate the central nervous system during experimental autoimmune encephalomyelitis (EAE), and Thrb is exclusively expressed in IL-17-producing CD4+ T cells (Th17 cells) that develop both in vitro or in vivo. Sobetirome, a selective TR-β agonist, promoted pathogenic Th17 differentiation and IL-17 production in the presence of exogenous IL-1β. Conversely, small interfering RNA (siRNA)-mediated silencing of TR-β reduced IL-17 production, further supporting a T cell-intrinsic role of TR-β. Because C75, an inhibitor of de novo lipogenesis, blocked Th17 cell differentiation by sobetirome, the influence of TR-β signaling on Th17 cell induction is likely to act via a de novo lipogenesis-dependent mechanism. Furthermore, blocking TR-βexpression by siRNA changed the balance of IL-10/IL-17 production in cultured splenocytes, favoring an IL-10 phenotype. In contrast, IL-10 production by T cells was attenuated by activating TR-β signaling with sobetirome. Finally, the manipulation of TR-β signaling altered the severity of autoimmune disease: blocking TR-β reduced passive EAE and enhancing TR-β increased active EAE. These effects were accompanied by corresponding changes in the IL-10/IL-17 balance in encephalitogenic CD4+ T cells. In summary, our results demonstrate that TR-β signaling controls pathogenic Th cell function and autoimmunity.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- International immunology
- 巻
- 37
- 号
- 12
- 開始ページ
- 789
- 終了ページ
- 803
- 出版年月
- 2025年12月24日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1093/intimm/dxaf045
- 共同研究・競争的資金等の研究課題
研究者
木村 敦子
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