{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Canales-Herrerias P"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","Crohn's & Colitis Foundation"],"pagination":["eadg7549"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11140591"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(94)"],"pubmed_abstract":["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<sup>+</sup>) 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<sup>+</sup>IgG<sup>+</sup> plasmablasts in circulation, as well as IgG<sup>+</sup> 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."],"journal":["Science immunology"],"pubmed_title":["Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis."],"pmcid":["PMC11140591"],"funding_grant_id":["R01 DK123749","T32 AI132152","R03 AI068044","U01 AI163064","R01 AI168044","DP1 DK130660","938100"],"pubmed_authors":["Onufer EJ","Randolph GJ","Wang A","Rosenstein A","Colombel JF","Erlich EC","Laurent T","Paulsen JD","Helmink BA","Seki A","Verstockt B","Al-Taie Z","Ganjian D","Livanos AE","Martin J","Petralia F","Nakadar MZ","Cossarini F","Mintz RL","Canales-Herrerias P","Reboldi A","Wong J","Taylor MD","Yajnik V","Cerutti A","Jha D","Mehandru S","Meringer H","Dawson T","Uzzan M","Raso F","Czepielewski RS","Sharma K","Chung G","Tokuyama M","Faith JJ","Ko HM","Tankelevich M","Juarez J","Dai D","Polydorides AD","Suarez-Farinas M","Dunn A","Krek A","Argmann C"],"additional_accession":[]},"is_claimable":false,"name":"Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.","description":"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<sup>+</sup>) 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<sup>+</sup>IgG<sup>+</sup> plasmablasts in circulation, as well as IgG<sup>+</sup> 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T11:52:16.579Z","creation":"2026-04-08T12:00:48.518Z"},"accession":"S-EPMC11140591","cross_references":{"pubmed":["38640252"],"doi":["10.1126/sciimmunol.adg7549"]}}