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

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

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 193(2018) vom: 25. Aug., Seite 24-32
1. Verfasser: Lord, James D (VerfasserIn)
Weitere Verfasser: Long, S Alice, Shows, Donna M, Thorpe, Jerill, Schwedhelm, Katherine, Chen, Janice, Kita, Mariko, Buckner, Jane H
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Crohn's disease FOXP3 Helios IL-2, IL-6, IL-7, IL-21 Integrin Stat Th1 mehr... Th2 Treg Vedolizumab cT(FH) Antibodies, Monoclonal, Humanized CXCR5 protein, human Cytokines FOXP3 protein, human Forkhead Transcription Factors Gastrointestinal Agents IKZF2 protein, human Inflammation Mediators Integrins Receptors, CXCR5 integrin alpha4beta7 Ikaros Transcription Factor 148971-36-2 vedolizumab 9RV78Q2002
Beschreibung
Zusammenfassung:Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 27.08.2019
Date Revised 27.08.2019
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2018.05.006