IL-22 promotes mucin-type O-glycosylation and MATH1+ cell-mediated amelioration of intestinal inflammation

Ankita Singh; Michael Beaupre; Cecilia Villegas-Novoa; Kiyoshi Shiomitsu; Stephen J Gaudino; Suzanne Tawch; Ruhee Damle; Cody Kempen; Biswa Choudhury; Jeremy P McAleer; Brian S Sheridan; Paula Denoya; Richard S Blumberg; Patrick Hearing; Nancy L Allbritton; Pawan Kumar

doi:10.1016/j.celrep.2024.114206

IL-22 promotes mucin-type O-glycosylation and MATH1⁺ cell-mediated amelioration of intestinal inflammation

Cell Rep. 2024 May 10;43(5):114206. doi: 10.1016/j.celrep.2024.114206. Online ahead of print.

Authors

Ankita Singh¹, Michael Beaupre¹, Cecilia Villegas-Novoa², Kiyoshi Shiomitsu¹, Stephen J Gaudino¹, Suzanne Tawch¹, Ruhee Damle¹, Cody Kempen¹, Biswa Choudhury³, Jeremy P McAleer⁴, Brian S Sheridan¹, Paula Denoya⁵, Richard S Blumberg⁶, Patrick Hearing¹, Nancy L Allbritton², Pawan Kumar⁷

Affiliations

¹ Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
² Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
³ GlycoAnalytics Core, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Department of Pharmaceutical Sciences, Marshall University School of Pharmacy, Huntington, WV 25701, USA.
⁵ Division of Colon and Rectal Surgery, Department of Surgery, Stony Brook University Hospital, Stony Brook, NY 11794, USA.
⁶ Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁷ Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: pawan.kumar@stonybrook.edu.

PMID: 38733584
DOI: 10.1016/j.celrep.2024.114206

Abstract

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 Il22Ra1^IEC 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.

Keywords: B3GALT5; CP: Immunology; IL-22; IL-22Ra1; MATH1; O-glycan; STAT3; colitis; epithelium; mucin; regeneration.