Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection

Mahapatro M, Försch S, Hefele M, He GW, Giner-Ventura E, Mchedlidze T, Kindermann M, Vetrano S, Danese S, Günther C, Neurath M, Wirtz S, Becker C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 15

Pages Range: 1743-56

Journal Issue: 8

DOI: 10.1016/j.celrep.2016.04.049

Abstract

The intestinal epithelium constitutes an efficient barrier against the microbial flora. Here, we demonstrate an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. IL-33 was produced upon microbial challenge by a distinct population of pericryptal fibroblasts neighboring the intestinal stem cell niche. IL-33 programmed the differentiation of epithelial progenitors toward secretory IEC including Paneth and goblet cells. Finally, IL-33 suppressed Notch signaling in epithelial cells and induced expression of transcription factors governing differentiation into secretory IEC. In summary, we demonstrate that gut pericryptal fibroblasts release IL-33 to translate bacterial infection into an epithelial response to promote antimicrobial defense.

Authors with CRIS profile

Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Istituto Clinico Humanitas IT Italy (IT) University of València / Universitat de València ES Spain (ES)

How to cite

APA:

Mahapatro, M., Försch, S., Hefele, M., He, G.-W., Giner-Ventura, E., Mchedlidze, T.,... Becker, C. (2016). Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection. Cell Reports, 15(8), 1743-56. https://dx.doi.org/10.1016/j.celrep.2016.04.049

MLA:

Mahapatro, Mousumi, et al. "Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection." Cell Reports 15.8 (2016): 1743-56.

BibTeX: Download