2. Academic Validation
  3. Antibody secreting cells are critically dependent on integrin α4β7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis

Antibody secreting cells are critically dependent on integrin α4β7/MAdCAM-1 for intestinal recruitment and control of the microbiota during chronic colitis

  • Mucosal Immunol. 2022 Jan;15(1):109-119. doi: 10.1038/s41385-021-00445-z.
Christopher J Tyler 1 2,  Mauricio Guzman 1 2,  Luke R Lundborg 1 2,  Shaila Yeasmin 1 2,  Nadia Zgajnar 1 2,  Paul Jedlicka 3,  Giorgos Bamias 4,  Jesús Rivera-Nieves 5 6
Affiliations

Affiliations

  • 1 San Diego VA Medical Center, San Diego, CA, USA.
  • 2 Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
  • 3 Department of Pathology, University of Colorado Denver, Denver, CO, USA.
  • 4 GI Unit, 3rd Academic Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Athens, Greece.
  • 5 San Diego VA Medical Center, San Diego, CA, USA. jriveranieves@ucsd.edu.
  • 6 Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. jriveranieves@ucsd.edu.
PMID: 34433904 DOI: 10.1038/s41385-021-00445-z
Abstract

T and B cells employ Integrin α4β7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on α4β7 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 α4β7 Integrin during chronic colitis using IL-10-/- mice, β7-deficient IL-10-/-, IgA-deficient IL-10-/- mice, and antibody blockade of MAdCAM-1. We found that α4β7 was predominantly expressed by B cells. β7 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 β7-deficient IL-10-/- mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the β7-deficient state. Given the critical/nonredundant dependence of IgA ASC on α4β7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies.

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