2. Academic Validation
  3. Stroma-specific IL-15 coordinates epithelial IL-15Rα to promote intestinal epithelial repair

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

  • Sci China Life Sci. 2025 Oct 14. doi: 10.1007/s11427-024-2923-2.
Qihang Hou # 1 2,  Yong Zhang # 3,  Lihua Zhao # 1,  Yujiao Lai 1,  Junyou Li 4,  Yunshan Zhao 5,  Yang Yang 5,  Xin Yang 2,  Xiaojun Yang 2,  Bingkun Zhang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science & Technology, China Agricultural University, Beijing, 100193, China.
  • 2 College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
  • 3 Senior Department of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China.
  • 4 Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, 319-0206, Japan.
  • 5 DarkJade Sciences, Inc., Beijing, 100192, China.
  • 6 State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science & Technology, China Agricultural University, Beijing, 100193, China. bingkunzhang@126.com.
  • # Contributed equally.
PMID: 41107660 DOI: 10.1007/s11427-024-2923-2
Abstract

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.

Keywords

5-FU; IL-15/IL-15Rα; intestinal stromal cell; organoid; regeneration.

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