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<p>Interleukin (IL)-15 is critical for intestinal homeostasis, but the precise origin and functions of IL-15 involved in inflamed mucosal healing are not fully understood. This study demonstrated that IL-15/IL-15Rα signaling was up-regulated during wound healing in 5-fluorouracil (5-FU)-induced intestinal mucositis. Moreover, a subset of podoplanin<sup>+</sup> stromal cells located adjacent to crypts were the primary cellular source of IL-15 following gut damage. Stroma-specific IL-15 proved to be crucial for the regeneration of damaged intestine. The deletion of IL-15Rα in intestinal epithelial cells compromised the recovery from intestinal injury. Moreover, compared with IL-15, IL-15/IL-15Rα complex can more efficiently promote intestinal epithelial repair. When stimulating human-derived ileal organoids, IL-15/IL-15 complex induced epithelial proliferation through an STAT3-HIF-1α signaling axis and afforded protection against 5-FU-induced epithelial damage. These findings innovatively demonstrated that stroma-specific IL-15 coordinates epithelial IL-15Rα to accelerate wound healing in response to gut damage.</p>

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Stroma-specific IL-15 coordinates epithelial IL-15Rα to promote intestinal epithelial repair

  • 期刊论文

  • 发表日期：

    2025年10月14日

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  • Qihang Hou,
  • Yong Zhang,
  • Lihua Zhao,
  • Yujiao Lai,
  • Junyou Li,
  • Yunshan Zhao,
  • Yang Yang,
  • Xin Yang,
  • Xiaojun Yang,
  • Bingkun Zhang

摘要

Interleukin (IL)-15 is critical for intestinal homeostasis, but the precise origin and functions of IL-15 involved in inflamed mucosal healing are not fully understood. This study demonstrated that IL-15/IL-15Rα signaling was up-regulated during wound healing in 5-fluorouracil (5-FU)-induced intestinal mucositis. Moreover, a subset of podoplanin+ stromal cells located adjacent to crypts were the primary cellular source of IL-15 following gut damage. Stroma-specific IL-15 proved to be crucial for the regeneration of damaged intestine. The deletion of IL-15Rα in intestinal epithelial cells compromised the recovery from intestinal injury. Moreover, compared with IL-15, IL-15/IL-15Rα complex can more efficiently promote intestinal epithelial repair. When stimulating human-derived ileal organoids, IL-15/IL-15 complex induced epithelial proliferation through an STAT3-HIF-1α signaling axis and afforded protection against 5-FU-induced epithelial damage. These findings innovatively demonstrated that stroma-specific IL-15 coordinates epithelial IL-15Rα to accelerate wound healing in response to gut damage.