Interleukin-33 Potentiates TGF-β Signaling to Regulate Intestinal Stem Cell Regeneration After Radiation Injury

• Published in: Cell transplantation Vol. 32; p. 9636897231177377
• Main Authors: Guan, Ruoyu, Pan, Mengxue, Xu, Xiaoya, Du, Lixia, Rao, Xinxin, Fu, Guoxiang, Lv, Tao, Zhang, Long, Li, Yuanchuang, Tang, Peiyuan, Zhou, Yi, Wang, Yanqing, Zhang, Zhen, Gao, Jianjun, Zhou, Hong, Mi, Wenli, Hua, Guoqiang
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2023; Sage Publications Ltd; SAGE Publishing
• Subjects: Cell activation; Cell differentiation; Humans; Interleukin-1 Receptor-Like 1 Protein - metabolism; Interleukin-33 - metabolism; Intestine; Intestines; Organoids; Original; Radiation Injuries - therapy; Stem Cells; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; radiation; regeneration; IL-33; intestinal stem cells; GI syndrome
• ISSN: 0963-6897; 1555-3892
• DOI: 10.1177/09636897231177377

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal radiation injury. Accumulating evidence indicates that the interleukin family members play critical roles in intestinal stem-cell-mediated epithelial regeneration. However, little is known about the relationship between interleukin 33 (IL-33)/ST2 axis and intestinal regeneration after radiation injury. We demonstrate here that IL-33 expression significantly increased after radiation treatment. Deficiency of IL-33/ST2 promotes intestinal epithelial regeneration, resulting in a reduction of mortality during radiation-induced intestine injury. Using ex vivo organoid cultures, we show that recombinant IL-33 promotes intestinal stem cell differentiation. Mechanistically, the effects of IL-33 were mediated by activation of transforming growth factor-β signaling. Our findings reveal a fundamental mechanism by which IL-33 is able to regulate the intestinal crypt regeneration after tissue damage.