TY - JOUR
T1 - Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis
AU - Canales-Herrerias, Pablo
AU - Uzzan, Mathieu
AU - Seki, Akihiro
AU - Czepielewski, Rafael S.
AU - Verstockt, Bram
AU - Livanos, Alexandra E.
AU - Raso, Fiona
AU - Dunn, Alexandra
AU - Dai, Daniel
AU - Wang, Andrew
AU - Al-Taie, Zainab
AU - Martin, Jerome
AU - Laurent, Thomas
AU - Ko, Huaibin M.
AU - Tokuyama, Minami
AU - Tankelevich, Michael
AU - Meringer, Hadar
AU - Cossarini, Francesca
AU - Jha, Divya
AU - Krek, Azra
AU - Paulsen, John D.
AU - Taylor, Matthew D.
AU - Nakadar, Mohammad Zuber
AU - Wong, Joshua
AU - Erlich, Emma C.
AU - Mintz, Rachel L.
AU - Onufer, Emily J.
AU - Helmink, Beth A.
AU - Sharma, Keshav
AU - Rosenstein, Adam
AU - Ganjian, Danielle
AU - Chung, Grace
AU - Dawson, Travis
AU - Juarez, Julius
AU - Yajnik, Vijay
AU - Cerutti, Andrea
AU - Faith, Jeremiah J.
AU - Suarez-Farinas, Mayte
AU - Argmann, Carmen
AU - Petralia, Francesca
AU - Randolph, Gwendalyn J.
AU - Polydorides, Alexandros D.
AU - Reboldi, Andrea
AU - Colombel, Jean Frederic
AU - Mehandru, Saurabh
N1 - Publisher Copyright:
© 2024 American Association for the Advancement of Science. All rights reserved.
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85191104135&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.adg7549
DO - 10.1126/sciimmunol.adg7549
M3 - Article
C2 - 38640252
AN - SCOPUS:85191104135
SN - 2470-9468
VL - 9
JO - Science immunology
JF - Science immunology
IS - 94
M1 - eadg7549
ER -