细胞生物学
祖细胞
炎症性肠病
结肠炎
粘蛋白
炎症
免疫学
化学
干细胞
生物
癌症研究
医学
病理
生物化学
疾病
作者
Ankita Singh,Michael Beaupre,Cecilia Villegas-Novoa,Keijiro Shiomitsu,Stephen Gaudino,Suzanne Tawch,Rashmin Damle,Cody Kempen,Biswa Choudhury,Jeremy P. McAleer,Brian S. Sheridan,Paula Denoya,Richard S. Blumberg,Patrick Hearing,Nancy L. Allbritton,Pawan Kumar
出处
期刊:Cell Reports
[Elsevier]
日期:2024-05-01
卷期号:43 (5): 114206-114206
标识
DOI:10.1016/j.celrep.2024.114206
摘要
The interleukin (IL)-22 cytokine can be protective or inflammatory in the intestine. It is unclear if IL-22 receptor (IL-22Ra1)-mediated protection involves a specific type of intestinal epithelial cell (IEC). By using a range of IEC type-specific Il22Ra1 conditional knockout mice and a dextran sulfate sodium (DSS) colitis model, we demonstrate that IL-22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue regeneration. The IL-22Ra1 signaling in IECs promotes mucin core-2 O-glycan extension and induces beta-1,3-galactosyltransferase 5 (B3GALT5) expression in the colon. Adenovirus-mediated expression of B3galt5 is sufficient to rescue Il22Ra1IEC mice from DSS colitis. Additionally, we observe a reduction in the expression of B3GALT5 and the Tn antigen, which indicates defective mucin O-glycan, in the colon tissue of patients with ulcerative colitis. Lastly, IL-22Ra1 signaling in MATH1+ progenitor cells promotes organoid regeneration after DSS injury. Our findings suggest that IL-22-dependent protective responses involve O-glycan modification, proliferation, and differentiation in MATH1+ progenitor cells.
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