Scholarlink

<p>Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanisms underlying this association remain unknown. To systematically investigate the role of zinc in CD4<sup>+</sup> T cell fate determination and intestinal homeostasis, we evaluated its immunomodulatory dynamics using a murine colitis model alongside in vitro differentiation assays employing human primary naive CD4<sup>+</sup> T cells. We found that zinc supplementation remarkably ameliorated experimental mucosal damage by abruptly halting the local infiltration of pathogenic CD4<sup>+</sup> T cells. Both in vivo and in vitro analyses revealed that zinc does not merely stall T cell polarization, but actively sensitizes these effector subsets to cell demise. Comprehensive transcriptomic sequencing pinpointed the ferroptosis cascade as the critical mediator of this clearance mechanism. Specifically, zinc systematically suppressed T cell anti-ferroptotic defenses by downregulating GPX4 and SLC7A11, while concurrently amplifying pro-ferroptotic drivers such as ACSL4. This targeted metabolic stress profoundly sensitized hyperactive T cells to ferroptosis, effectively purging the inflammatory mucosal niche. Ultimately, these findings reframe the fundamental role of zinc in intestinal immune homeostasis, exposing ferroptosis as a druggable vulnerability in IBD and providing a strong mechanistic rationale for zinc-based clinical interventions.</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

Zinc supplementation ameliorates colitis in mice by sensitizing pathogenic CD4+ T cells to ferroptosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月17日

查看全文
  • Zongkuo Li,
  • Jianting Cai

摘要

Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanisms underlying this association remain unknown. To systematically investigate the role of zinc in CD4+ T cell fate determination and intestinal homeostasis, we evaluated its immunomodulatory dynamics using a murine colitis model alongside in vitro differentiation assays employing human primary naive CD4+ T cells. We found that zinc supplementation remarkably ameliorated experimental mucosal damage by abruptly halting the local infiltration of pathogenic CD4+ T cells. Both in vivo and in vitro analyses revealed that zinc does not merely stall T cell polarization, but actively sensitizes these effector subsets to cell demise. Comprehensive transcriptomic sequencing pinpointed the ferroptosis cascade as the critical mediator of this clearance mechanism. Specifically, zinc systematically suppressed T cell anti-ferroptotic defenses by downregulating GPX4 and SLC7A11, while concurrently amplifying pro-ferroptotic drivers such as ACSL4. This targeted metabolic stress profoundly sensitized hyperactive T cells to ferroptosis, effectively purging the inflammatory mucosal niche. Ultimately, these findings reframe the fundamental role of zinc in intestinal immune homeostasis, exposing ferroptosis as a druggable vulnerability in IBD and providing a strong mechanistic rationale for zinc-based clinical interventions.