| First Author | Tyler CJ | Year | 2022 |
| Journal | Mucosal Immunol | Volume | 15 |
| Issue | 1 | Pages | 109-119 |
| PubMed ID | 34433904 | Mgi Jnum | J:341295 |
| Mgi Id | MGI:7431342 | Doi | 10.1038/s41385-021-00445-z |
| Citation | Tyler CJ, et al. (2022) Antibody secreting cells are critically dependent on integrin alpha4beta7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis. Mucosal Immunol 15(1):109-119 |
| abstractText | T and B cells employ integrin alpha4beta7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on alpha4beta7 for homing during inflammatory conditions has not been fully examined. This may have implications for our understanding of the mode of action of anti-integrin therapies in inflammatory bowel disease (IBD). Here, we examined the role of alpha4beta7 integrin during chronic colitis using IL-10(-/-) mice, beta7-deficient IL-10(-/-), IgA-deficient IL-10(-/-) mice, and antibody blockade of MAdCAM-1. We found that alpha4beta7 was predominantly expressed by B cells. beta7 deficiency and MAdCAM-1 blockade specifically depleted antibody secreting cells (ASC) (not T cells) from the colonic LP, leading to a fecal pan-immunoglobulin deficit, severe colitis, and alterations of microbiota composition. Colitis was not due to defective regulation, as dendritic cells (DC), regulatory T cells, retinaldehyde dehydrogenase (RALDH) expression, activity, and regulatory T/B-cell cytokines were all comparable between the strains/treatment. Finally, an IgA deficit closely recapitulated the clinical phenotype and altered microbiota composition of beta7-deficient IL-10(-/-) mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the beta7-deficient state. Given the critical/nonredundant dependence of IgA ASC on alpha4beta7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies. |
