Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8721239 | Clinical Immunology | 2018 | 30 Pages |
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 FOXP3â¯+â¯Helios+ thymically-derived Tregs (tTregs) than FOXP3â¯+â¯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.
Keywords
FOXP3type 1 helper T cellType 2 helper T celltype 17 helper T celltTregcTfhTh2Th1HBITh17TregEDSSIBDPBMCMFITCrSTATinterleukinIntegrinCrohn's diseaseInflammatory bowel diseaseRegulatory T cellperipheral blood mononuclear cellsMultiple sclerosismean fluorescence intensityHeliosVedolizumabC reactive proteinCRPT cell receptor
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Authors
James D. Lord, S. Alice Long, Donna M. Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H. Buckner,