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

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.

SUBMITTER: Singh A

PROVIDER: S-EPMC11328608 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

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IL-22 promotes mucin-type O-glycosylation and MATH1<sup>+</sup> cell-mediated amelioration of intestinal inflammation.

Singh Ankita A Beaupre Michael M Villegas-Novoa Cecilia C Shiomitsu Kiyoshi K Gaudino Stephen J SJ Tawch Suzanne S Damle Ruhee R Kempen Cody C Choudhury Biswa B McAleer Jeremy P JP Sheridan Brian S BS Denoya Paula P Blumberg Richard S RS Hearing Patrick P Allbritton Nancy L NL Kumar Pawan P

Cell reports 20240511 5

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<sup>+</sup> cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue r ...[more]

PMID: 38733584

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Project description:BackgroundSerum IL-22 levels are increased in patients with atopic dermatitis, which commonly precedes asthma in the atopic march. Epicutaneous sensitization in mice results in TH2-dominated skin inflammation that mimics atopic dermatitis and sensitizes the airways for antigen challenge-induced allergic inflammation characterized by the presence of both eosinophils and neutrophils. Epicutaneous sensitization results in increased serum levels of IL-22.ObjectiveWe sought to determine the role of IL-22 in antigen-driven airway allergic inflammation after inhalation challenge in epicutaneously sensitized mice.MethodsWild-type (WT) and Il22-/- mice were sensitized epicutaneously or immunized intraperitoneally with ovalbumin (OVA) and challenged intranasally with antigen. OVA T-cell receptor-specific T cells were TH22 polarized in vitro. Airway inflammation, mRNA levels in the lungs, and airway hyperresponsiveness (AHR) were examined.ResultsEpicutaneous sensitization preferentially elicited an IL-22 response compared with intraperitoneal immunization. Intranasal challenge of mice epicutaneously sensitized with OVA elicited in the lungs Il22 mRNA expression, IL-22 production, and accumulation of CD3+CD4+IL-22+ T cells that coexpressed IL-17A and TNF-α. Epicutaneously sensitized Il22-/- mice exhibited diminished eosinophil and neutrophil airway infiltration and decreased AHR after intranasal OVA challenge. Production of IL-13, IL-17A, and TNF-α was normal, but IFN-γ production was increased in lung cells from airway-challenged and epicutaneously sensitized Il22-/- mice. Intranasal instillation of IFN-γ-neutralizing antibody partially reversed the defect in eosinophil recruitment. WT recipients of TH22-polarized WT, but not IL-22-deficient, T-cell receptor OVA-specific T cells, which secrete both IL-17A and TNF-α, had neutrophil-dominated airway inflammation and AHR on intranasal OVA challenge. Intranasal instillation of IL-22 with TNF-α, but not IL-17A, elicited neutrophil-dominated airway inflammation and AHR in WT mice, suggesting that loss of IL-22 synergy with TNF-α contributed to defective recruitment of neutrophils into the airways of Il22-/- mice. TNF-α, but not IL-22, blockade at the time of antigen inhalation challenge inhibited airway inflammation in epicutaneously sensitized mice.ConclusionEpicutaneous sensitization promotes generation of antigen-specific IL-22-producing T cells that promote airway inflammation and AHR after antigen challenge, suggesting that IL-22 plays an important role in the atopic march.

Dataset Information

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

Publications

IL-22 promotes mucin-type O-glycosylation and MATH1<sup>+</sup> cell-mediated amelioration of intestinal inflammation.

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Dataset Information

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

Publications

IL-22 promotes mucin-type O-glycosylation and MATH1<sup>+</sup> cell-mediated amelioration of intestinal inflammation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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