2. Academic Validation
  3. IL-22 promotes mucin-type O-glycosylation and MATH1+ cell-mediated amelioration of intestinal inflammation

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

  • Cell Rep. 2024 May 28;43(5):114206. doi: 10.1016/j.celrep.2024.114206.
Ankita Singh 1,  Michael Beaupre 1,  Cecilia Villegas-Novoa 2,  Kiyoshi Shiomitsu 1,  Stephen J Gaudino 1,  Suzanne Tawch 1,  Ruhee Damle 1,  Cody Kempen 1,  Biswa Choudhury 3,  Jeremy P McAleer 4,  Brian S Sheridan 1,  Paula Denoya 5,  Richard S Blumberg 6,  Patrick Hearing 1,  Nancy L Allbritton 2,  Pawan Kumar 7
Affiliations

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 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.

Keywords

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

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