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Circulating integrin alpha4/beta7+ lymphocytes targeted by vedolizumab have a pro-inflammatory phenotype.

Authors
  • Lord, James D1
  • Long, S Alice2
  • Shows, Donna M2
  • Thorpe, Jerill2
  • Schwedhelm, Katherine2
  • Chen, Janice2
  • Kita, Mariko2
  • Buckner, Jane H2
  • 1 Benaroya Research Institute, Translational Research Program, United States.. Electronic address: [email protected] , (United States)
  • 2 Benaroya Research Institute, Translational Research Program, United States. , (United States)
Type
Published Article
Journal
Clinical Immunology
Publisher
Elsevier
Publication Date
Aug 01, 2018
Volume
193
Pages
24–32
Identifiers
DOI: 10.1016/j.clim.2018.05.006
PMID: 29842945
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells. Integrin alpha4/beta7+ CD4 T cells were also rare among cells expressing the Th2 marker CRTh2, but enriched in cells bearing the circulating T follicular helper cell marker CXCR5. Thus the effect of this anti-integrin therapy on the mucosal immune system may be more qualitative than quantitative, and selectively replace pro-inflammatory effector cells with Tregs and Th2 cells to facilitate immune tolerance in the mucosa without globally depleting lymphocytes from the intestinal mucosa. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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