biostudies-literatureCanales-Herrerias PNIDDK NIH HHSNIAID NIH HHSCrohn's & Colitis Foundationeadg7549https://www.ebi.ac.uk/biostudies/studies/S-EPMC11140591biostudies-literatureUnknown9(94)Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7⁺) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7⁺IgG⁺ plasmablasts in circulation, as well as IgG⁺ plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.Science immunologyGut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.PMC11140591R01 DK123749T32 AI132152R03 AI068044U01 AI163064R01 AI168044DP1 DK130660938100Onufer EJRandolph GJWang ARosenstein AColombel JFErlich ECLaurent TPaulsen JDHelmink BASeki AVerstockt BAl-Taie ZGanjian DLivanos AEMartin JPetralia FNakadar MZCossarini FMintz RLCanales-Herrerias PReboldi AWong JTaylor MDYajnik VCerutti AJha DMehandru SMeringer HDawson TUzzan MRaso FCzepielewski RSSharma KChung GTokuyama MFaith JJKo HMTankelevich MJuarez JDai DPolydorides ADSuarez-Farinas MDunn AKrek AArgmann CfalseGut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7⁺) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7⁺IgG⁺ plasmablasts in circulation, as well as IgG⁺ plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.2024-01-01T00:00:00Z2024 Apr2026-06-01T11:52:16.579Z2026-04-08T12:00:48.518ZS-EPMC111405913864025210.1126/sciimmunol.adg7549