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.

循环淋巴细胞上的整合素alpha4 / beta7将其识别为肠道嗜性蛋白，可被人源化抗体vedolizumab靶向治疗炎症性肠病（IBD）。我们发现表达α4/β7的淋巴细胞对促炎性细胞因子IL-6，IL-7和IL-21的响应明显更高，对支持调节性T细胞（Treg）的细胞因子IL-2的响应则更低。与FOXP3 + Helios-外周血Tregs（pTregs）或FOXP3效应T细胞相比，FOXP3 + Helios +胸腺来源的Tregs（tTregs）所占的百分比更低。整合素α4/β7+ CD4 T细胞在表达Th2标记CRTh2的细胞中也很少，但富含带有循环T滤泡辅助细胞标记CXCR5的细胞。