T and B cells employ integrin α4β7 to migrate to intestine under homeostatic conditions. Whether those cells differentially rely on α4β7 for homing during inflammatory conditions has not been fully examined. This may have implications for our understanding of the mode of action of anti-integrin therapies in inflammatory bowel disease (IBD). Here, we examined the role of α4β7 integrin during chronic colitis using IL-10^−/− mice, β7-deficient IL-10^−/−, IgA-deficient IL-10^−/− mice, and antibody blockade of MAdCAM-1. We found that α4β7 was predominantly expressed by B cells. β7 deficiency and MAdCAM-1 blockade specifically depleted antibody secreting cells (ASC) (not T cells) from the colonic LP, leading to a fecal pan-immunoglobulin deficit, severe colitis, and alterations of microbiota composition. Colitis was not due to defective regulation, as dendritic cells (DC), regulatory T cells, retinaldehyde dehydrogenase (RALDH) expression, activity, and regulatory T/B-cell cytokines were all comparable between the strains/treatment. Finally, an IgA deficit closely recapitulated the clinical phenotype and altered microbiota composition of β7-deficient IL-10^−/− mice. Thus, a luminal IgA deficit contributes to accelerated colitis in the β7-deficient state. Given the critical/nonredundant dependence of IgA ASC on α4β7:MAdCAM-1 for intestinal homing, B cells may represent unappreciated targets of anti-integrin therapies.

T 细胞和 B 细胞利用整合素 α4β7 在稳态条件下迁移至肠道。这些细胞在炎症条件下是否不同地依赖 α4β7 归巢尚未得到充分研究。这可能对我们理解炎症性肠病 (IBD) 中抗整合素疗法的作用方式有影响。^{在这里，我们使用 IL-10 -/-}小鼠、β7 缺陷型 IL-10 ^-/-、IgA 缺陷型 IL-10 ^-/-检测了 α4β7 整合素在慢性结肠炎期间的作用小鼠和 MAdCAM-1 的抗体阻断。我们发现 α4β7 主要由 B 细胞表达。β7 缺乏和 MAdCAM-1 阻断特异性耗尽结肠 LP 中的抗体分泌细胞 (ASC)（不是 T 细胞），导致粪便泛免疫球蛋白缺陷、严重结肠炎和微生物群组成的改变。结肠炎不是由于调节缺陷引起的，因为树突状细胞 (DC)、调节性 T 细胞、视黄醛脱氢酶 (RALDH) 表达、活性和调节性 T/B 细胞因子在菌株/治疗之间都具有可比性。最后，IgA 缺陷密切概括了 β7 缺陷型 IL-10 的临床表型和改变的微生物群组成^-/-老鼠。因此，管腔 IgA 缺陷会加速 β7 缺陷状态下的结肠炎。鉴于 IgA ASC 对用于肠道归巢的 α4β7:MAdCAM-1 的关键/非冗余依赖性，B 细胞可能是抗整合素疗法未被重视的靶标。