Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis

Gámez Belmonte MdlR, Wagner Y, Mahapatro M, Wang R, Erkert L, Gonzalez Acera M, Cineus R, Hainbuch S, Patankar J, Vöhringer D, Hegazy AN, Neurath M, Wirtz S, Becker C (2024)

Publication Language: English

Publication Type: Journal article, Original article

Publication year: 2024

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 14

Article Number: 26522

DOI: 10.1038/s41598-024-78336-z

Abstract

Gasdermin C is one of the least studied members of the gasdermin family of proteins, known for their critical involvement in pyroptosis and host defense. Furthermore, evidence for the role of Gasdermin C in the intestine is scarce and partly controversial. Here, we tested the functional role of Gasdermin C in intestinal homeostasis, inflammation and tumorigenesis. : We studied Gasdermin C in response to cytokines in intestinal organoids. We evaluated epithelial differentiation, cell death and immune infiltration under steady state conditions in a new mouse line deficient in Gasdermin C. The role of Gasdermin C was analyzed in acute colitis, infection and colitis-associated cancer. Gasdemin C is highly expressed in the intestinal epithelium and strongly induced by the type 2 cytokines IL-4 and IL-13 in a STAT6-dependent manner. Gasdermin C-deficient mice show no changes in tissue architecture and epithelial homeostasis. Epithelial organoids deficient in Gasdermin C develop normally and show no alterations in proliferation or cell death. No changes were found in models of acute colitis, type 2 intestinal infection and colitis-associated cancer. Gasdermin C genes are upregulated by type 2 immunity, yet appear dispensable for the development of intestinal inflammation, infection and colitis-associated cancer.

Authors with CRIS profile

Maria de los Reyes Gámez Belmonte Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Ru Wang Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Lena Erkert Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Miguel Gonzalez Acera Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology David Vöhringer Professur für Infektionsabwehr und Toleranz Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Leibniz-Gemeinschaft DE Germany (DE)

How to cite

APA:

Gámez Belmonte, M.d.l.R., Wagner, Y., Mahapatro, M., Wang, R., Erkert, L., Gonzalez Acera, M.,... Becker, C. (2024). Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis. Scientific Reports, 14. https://doi.org/10.1038/s41598-024-78336-z

MLA:

Gámez Belmonte, Maria de los Reyes, et al. "Intestinal epithelial Gasdermin C is induced by IL-4R/STAT6 signaling but is dispensable for gut immune homeostasis." Scientific Reports 14 (2024).

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