β7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon

Mucosal Immunology
A SchippersN Wagner

Abstract

Leukocyte recruitment is pivotal for the initiation and perpetuation of inflammatory bowel disease (IBD) and controlled by the specificity and interactions of chemokines and adhesion molecules. Interactions of the adhesion molecules α4β7-integrin and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) promote the accumulation of pathogenic T-cell populations in the inflamed intestine. We aimed to elucidate the significance of β7-integrin expression on innate immune cells for the pathogenesis of IBD. We demonstrate that β7-integrin deficiency protects recombination-activating gene-2 (RAG-2)-deficient mice from dextran sodium sulfate (DSS)-induced colitis and coincides with decreased numbers of colonic effector monocytes. We also show that β7-integrin is expressed on most CD11b(+)CD64(low)Ly6C(+) bone marrow progenitors and contributes to colonic recruitment of these proinflammatory monocytes. Importantly, adoptive transfer of CD115(+) wild-type (WT) monocytes partially restored the susceptibility of RAG-2/β7-integrin double-deficient mice to DSS-induced colitis, thereby demonstrating the functional importance of β7-integrin-expressing monocytes for the development of DSS colitis. We also reveal that genetic ablation of MAdCAM-...Continue Reading

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Citations

Sep 24, 2016·Journal of Crohn's & Colitis·Carolijn SmidsEllen G van Lochem
Jun 25, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Aoife M O'DwyerStephen J Keely
Feb 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zoltán KellermayerPéter Balogh
Sep 14, 2017·Current Opinion in Gastroenterology·Giorgos BamiasFabio Cominelli
Oct 26, 2018·Scientific Reports·Sachiko YamaguchiSusumu Nakae
Dec 29, 2018·Blood Advances·Eun Jeong ParkMotomu Shimaoka
Dec 13, 2018·Frontiers in Immunology·Calum C Bain, Anika Schridde
Jul 12, 2020·International Journal of Molecular Sciences·Greta CapraraMarco Erreni
Mar 13, 2019·Journal of Crohn's & Colitis·Anna Rawa-GołębiewskaEdyta Zagórowicz
Dec 15, 2020·Cellular and Molecular Gastroenterology and Hepatology·Angela SchippersNorbert Wagner
Jan 13, 2021·Nature Communications·Nicolas RochereauStéphane Paul
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Matthew Luzentales-SimpsonLaura M Sly
Mar 20, 2021·Frontiers in Cell and Developmental Biology·Xuebing HanGang Liu
May 15, 2021·Journal of Crohn's & Colitis·Lijuan WangQifeng Yang
Sep 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Haruka TaniKiyoshi Takeda

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Methods Mentioned

BETA
flow cytometry
ELISA
FACS

Software Mentioned

7000 System SDS
FlowJo
GraphPad Prism

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