Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

ABSTRACT: Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system. Transcriptomic studies with protein level validation were used to study drug MOA using conventional and transgenic murine models. We found a significant decrease in colonic and ileal naïve B and T cells and circulating gut-homing plasmablasts (β7⁺) in VDZ-treated patients, pointing to gut-associated lymphoid tissue (GALT) targeting by VDZ. Murine Peyer's patches (PP) demonstrated a significant loss cellularity associated with red

SUBMITTER: Canales-Herrerias P 

PROVIDER: S-EPMC9882272 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature