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

Mousumi Mahapatro, Sebastian Foersch, Manuela Hefele, Gui Wei He, Elisa Giner-Ventura, Tamar Mchedlidze, Markus Kindermann, Stefania Vetrano, Silvio Danese, Claudia Günther, Markus F. Neurath, Stefan Wirtz, Christoph Becker

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1743-1756
Number of pages14
JournalCell Reports
Volume15
Issue number8
DOIs
Publication statusPublished - May 24 2016

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Fibroblasts
Infection
Paneth Cells
Stem Cell Niche
Salmonella
Goblet Cells
Salmonella typhimurium
Intestinal Mucosa
Stem cells
Bacterial Infections
Interleukin-33
Transcription Factors
Cell Count
Epithelial Cells
Population

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mahapatro, M., Foersch, 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), 1743-1756. https://doi.org/10.1016/j.celrep.2016.04.049

Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection. / Mahapatro, Mousumi; Foersch, Sebastian; Hefele, Manuela; He, Gui Wei; Giner-Ventura, Elisa; Mchedlidze, Tamar; Kindermann, Markus; Vetrano, Stefania; Danese, Silvio; Günther, Claudia; Neurath, Markus F.; Wirtz, Stefan; Becker, Christoph.

In: Cell Reports, Vol. 15, No. 8, 24.05.2016, p. 1743-1756.

Research output: Contribution to journalArticle

Mahapatro, M, Foersch, S, Hefele, M, He, GW, Giner-Ventura, E, Mchedlidze, T, Kindermann, M, Vetrano, S, Danese, S, Günther, C, Neurath, MF, Wirtz, S & Becker, C 2016, 'Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection', Cell Reports, vol. 15, no. 8, pp. 1743-1756. https://doi.org/10.1016/j.celrep.2016.04.049
Mahapatro, Mousumi ; Foersch, Sebastian ; Hefele, Manuela ; He, Gui Wei ; Giner-Ventura, Elisa ; Mchedlidze, Tamar ; Kindermann, Markus ; Vetrano, Stefania ; Danese, Silvio ; Günther, Claudia ; Neurath, Markus F. ; Wirtz, Stefan ; Becker, Christoph. / Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection. In: Cell Reports. 2016 ; Vol. 15, No. 8. pp. 1743-1756.
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