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

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 relat...

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Published in:Cell transplantation 2023-01, Vol.32, p.9636897231177377-9636897231177377
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: Article
Language:English
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
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container_start_page 9636897231177377
container_title Cell transplantation
container_volume 32
creator 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
description 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.
doi_str_mv 10.1177/09636897231177377
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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. 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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
title Interleukin-33 Potentiates TGF-β Signaling to Regulate Intestinal Stem Cell Regeneration After Radiation Injury
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