The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_39C99B303D1E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis.
Journal
Mucosal immunology
Author(s)
Wyss A., Raselli T., Perkins N., Ruiz F., Schmelczer G., Klinke G., Moncsek A., Roth R., Spalinger M.R., Hering L., Atrott K., Lang S., Frey-Wagner I., Mertens J.C., Scharl M., Sailer A.W., Pabst O., Hersberger M., Pot C., Rogler G., Misselwitz B.
ISSN
1935-3456 (Electronic)
ISSN-L
1933-0219
Publication state
Published
Issued date
05/2019
Peer-reviewed
Oui
Volume
12
Number
3
Pages
733-745
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis. Accordingly, we detected elevated levels of 25-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol in mice with acute colonic inflammation. Knockout of EBI2 or CH25H did not affect severity of DSS colitis; however, inflammation was decreased in male EBI2 <sup>-/-</sup> mice in the IL-10 colitis model. The colonic immune system comprises mucosal lymphoid structures, which accumulate upon chronic inflammation in IL-10-deficient mice and in chronic DSS colitis. However, EBI2 <sup>-/-</sup> mice formed significantly less colonic lymphoid structures at baseline and showed defects in inflammation-induced accumulation of lymphoid structures. In summary, we report induction of the EBI2-7α,25-dihydroxycholesterol axis in colitis and a role of EBI2 for the accumulation of lymphoid tissue during homeostasis and inflammation. These data implicate the EBI2-7α,25-dihydroxycholesterol axis in IBD pathogenesis.
Keywords
Immunology, Immunology and Allergy
Pubmed
Web of science
Open Access
Yes
Create date
06/03/2019 17:21
Last modification date
20/08/2019 13:29
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