| First Author | Schippers A | Year | 2016 |
| Journal | Mucosal Immunol | Volume | 9 |
| Issue | 2 | Pages | 527-38 |
| PubMed ID | 26349655 | Mgi Jnum | J:317941 |
| Mgi Id | MGI:6830370 | Doi | 10.1038/mi.2015.82 |
| Citation | Schippers A, et al. (2016) beta7-Integrin exacerbates experimental DSS-induced colitis in mice by directing inflammatory monocytes into the colon. Mucosal Immunol 9(2):527-38 |
| abstractText | 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 alpha4beta7-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 beta7-integrin expression on innate immune cells for the pathogenesis of IBD. We demonstrate that beta7-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 beta7-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/beta7-integrin double-deficient mice to DSS-induced colitis, thereby demonstrating the functional importance of beta7-integrin-expressing monocytes for the development of DSS colitis. We also reveal that genetic ablation of MAdCAM-1 ameliorates experimental colitis in RAG-2-deficient mice as well. In summary, we demonstrate a previously unknown role of alpha4beta7-integrin-MAdCAM-1 interactions as drivers of colitis by directing inflammatory monocytes into the colon. |
