Targeting interactions between α4β7 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses αEβ7 integrin, which is expressed on proinflammatory lymphocytes, to increase cell retention. The factors governing lymphocyte migration into the intestinal mucosa and αE integrin expression in healthy subjects and IBD patients remain incompletely understood. We evaluated changes in factors involved in lymphocyte migration and differentiation within tissues. Both ileal and colonic tissue from active IBD patients showed upregulation of ICAM-1, VCAM-1, and MAdCAM-1 at the gene and protein levels compared with healthy subjects and/or inactive IBD patients. β1 and β7 integrin expression on circulating lymphocytes was similar across groups. TGF-β1 treatment induced expression of αE on both β7⁺ and β7⁻ T cells, suggesting that cells entering the mucosa independently of MAdCAM-1/α4β7 can become αEβ7⁺. ITGAE gene polymorphisms did not alter protein induction following TGF-β1 stimulation. Increased phospho-SMAD3, which is directly downstream of TGF-β, and increased TGF-β–responsive gene expression were observed in the colonic mucosa of IBD patients. Finally, in vitro stimulation experiments showed that baseline β7 expression had little effect on cytokine, chemokine, transcription factor, and effector molecule gene expression in αE⁺ and αE⁻ T cells. These findings suggest cell migration to the gut mucosa may be altered in IBD and α4β7⁻, and α4β7⁺ T cells may upregulate αEβ7 in response to TGF-β once within the gut mucosa.

靶向 α4β7 整合素和内皮粘附分子 MAdCAM-1 之间的相互作用以抑制淋巴细胞迁移到胃肠道是炎症性肠病 (IBD) 的有效疗法。淋巴细胞进入粘膜后，这些细胞的一个子集表达 αEβ7 整合素，αEβ7 整合素在促炎淋巴细胞上表达，以增加细胞滞留。在健康受试者和 IBD 患者中控制淋巴细胞迁移到肠粘膜和αE 整合素表达的因素仍然不完全清楚。我们评估了参与组织内淋巴细胞迁移和分化的因素的变化。与健康受试者和/或非活动性 IBD 患者相比，活动性 IBD 患者的回肠和结肠组织在基因和蛋白质水平上均显示出 ICAM-1、VCAM-1 和 MAdCAM-1 的上调。各组循环淋巴细胞上 β1 和 β7 整联蛋白的表达相似。TGF-β1 处理诱导 β7 上的 αE 表达⁺和 β7 ^- T 细胞，表明独立于 MAdCAM-1/α4β7 进入粘膜的细胞可以变成 αEβ7 ⁺。TGF-β1 刺激后，ITGAE 基因多态性不改变蛋白质诱导。在 IBD 患者的结肠黏膜中观察到 TGF-β 直接下游的磷酸化 SMAD3 增加，以及 TGF-β 反应基因表达增加。最后，体外刺激实验表明基线β7表达对αE ⁺和αE ^- T细胞中的细胞因子、趋化因子、转录因子和效应分子基因表达几乎没有影响。这些发现表明细胞向肠粘膜的迁移可能在 IBD 和 α4β7 ^-和 α4β7 ^{+ 中}发生改变 T 细胞在肠道粘膜内可能会响应 TGF-β 上调 αEβ7。