IL-22-independent protection from colitis in the absence of Nkx2.3 transcription factor in mice

Zoltán Kellermayer, Dóra Vojkovics, Tareq Abu Dakah, Kornélia Bodó, Bálint Botz, Zsuzsanna Helyes, Gergely Berta, Béla Kajtár, Angela Schippers, Norbert Wagner, Luigi Scotto, Owen A. O'Connor, Hans Henning Arnold, Péter Balogh

Research output: Article

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Abstract

The transcription factor Nkx2.3 regulates the vascular specification of Peyer patches in mice through determining endothelial addressin preference and may function as a susceptibility factor in inflammatory bowel diseases in humans.We wished to analyze the role of Nkx2.3 in colonic solitary intestinal lymphoid tissue composition and in colitis pathogenesis. We studied the colonic solitary intestinal lymphoid tissue of Nkx2.3-deficient mice with immunofluorescence and flow cytometry. Colitis was induced in mice using 2.5% dextran sodium sulfate, and severity was assessed with histology, flow cytometry, and quantitative PCR. We found that the lack of Nkx2.3 impairs maturation of isolated lymphoid follicles and attenuates dextran sodium sulfate-induced colitis independent of endothelial absence of mucosal addressin cell-adhesion molecule-1 (MAdCAM-1), which was also coupled with enhanced colonic epithelial regeneration. Although we observed increased numbers of group 3 innate lymphoid cells and Th17 cells and enhanced transcription of IL-22, Ab-mediated neutralization of IL-22 did not abolish the protection from colitis in Nkx2.3-deficient mice. Nkx2.3 -/- hematopoietic cells could not rescue wild-type mice from colitis. Using LacZ-Nkx2.3 reporter mice, we found that Nkx2.3 expression was restricted to VAP-1+ myofibroblast-like pericryptal cells. These results hint at a previously unknown stromal role of Nkx2.3 as driver of colitis and indicate that Nkx2.3+ stromal cells play a role in epithelial cell homeostasis.

Original languageEnglish
Pages (from-to)1833-1844
Number of pages12
JournalJournal of Immunology
Volume202
Issue number6
DOIs
Publication statusPublished - jan. 1 2019

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kellermayer, Z., Vojkovics, D., Dakah, T. A., Bodó, K., Botz, B., Helyes, Z., Berta, G., Kajtár, B., Schippers, A., Wagner, N., Scotto, L., O'Connor, O. A., Arnold, H. H., & Balogh, P. (2019). IL-22-independent protection from colitis in the absence of Nkx2.3 transcription factor in mice. Journal of Immunology, 202(6), 1833-1844. https://doi.org/10.4049/jimmunol.1801117