Scholarlink

<p>Invariant natural killer T (iNKT) cells serve as a crucial bridge between innate and adaptive immunity, yet the molecular mechanisms that sustain their subset homeostasis remain incompletely defined. Here, we identify CD23 (FcεRII) as a previously unrecognized intrinsic regulator of NKT17 cell homeostasis. CD23 deficiency selectively diminished NKT17 frequency and IL-17 production in the thymus and spleen, while leaving NKT1 and NKT2 subsets largely unaffected. Loss of CD23 led to decreased IL-7Rα expression and impaired mTORC2-dependent phosphorylation of AKT (Ser473), accompanied by reduced Bcl-2 expression and increased apoptosis of NKT17 cells. Administration of exogenous IL-7 restored NKT17 abundance and IL-17 secretion in CD23-deficient mice without normalizing PLZF or RORγt expression, indicating that CD23 primarily supports metabolic and survival signaling rather than transcriptional programming. Collectively, these findings define CD23 as an upstream checkpoint of the IL-7Rα-mTORC2 axis that preserves NKT17 viability. By delineating a previously unrecognized link between cytokine and metabolic pathways, this study expands the molecular framework governing iNKT cell development and subset maintenance.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CD23 sustains NKT17 cell homeostasis via IL-7Rα-mTORC2 signaling

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月30日

查看全文
  • Linlin Niu,
  • Bingqian Tan,
  • Jingting Xu,
  • Guangwei Zhang,
  • Bo Wang,
  • Zuochen Du,
  • Di Yang,
  • Chengxi Zhuang,
  • Xiaoyu Du,
  • Yao Zhao

摘要

Invariant natural killer T (iNKT) cells serve as a crucial bridge between innate and adaptive immunity, yet the molecular mechanisms that sustain their subset homeostasis remain incompletely defined. Here, we identify CD23 (FcεRII) as a previously unrecognized intrinsic regulator of NKT17 cell homeostasis. CD23 deficiency selectively diminished NKT17 frequency and IL-17 production in the thymus and spleen, while leaving NKT1 and NKT2 subsets largely unaffected. Loss of CD23 led to decreased IL-7Rα expression and impaired mTORC2-dependent phosphorylation of AKT (Ser473), accompanied by reduced Bcl-2 expression and increased apoptosis of NKT17 cells. Administration of exogenous IL-7 restored NKT17 abundance and IL-17 secretion in CD23-deficient mice without normalizing PLZF or RORγt expression, indicating that CD23 primarily supports metabolic and survival signaling rather than transcriptional programming. Collectively, these findings define CD23 as an upstream checkpoint of the IL-7Rα-mTORC2 axis that preserves NKT17 viability. By delineating a previously unrecognized link between cytokine and metabolic pathways, this study expands the molecular framework governing iNKT cell development and subset maintenance.