Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama, Tsurumi, Yokohama, Japan.
Science. 2012 Apr 27;336(6080):485-9. doi: 10.1126/science.1217718.
Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed cell death-1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (T(FH)) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches. Consequently, the IgAs produced in PD-1-deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.
免疫球蛋白 A（IgA）对于维持肠道细菌群落与宿主免疫系统之间的共生平衡至关重要。在这里，我们提供的证据表明，抑制性共受体程序性细胞死亡蛋白-1（PD-1）通过适当选择 IgA 浆细胞库来调节肠道微生物群。PD-1 缺乏会产生大量表型改变的滤泡辅助性 T 细胞（T(FH)），导致派尔集合淋巴结生发中心中 IgA 前体细胞的选择失调。因此，PD-1 缺陷小鼠产生的 IgA 与细菌结合的能力降低，导致肠道微生物群落发生改变。因此，PD-1 在调节抗体多样性中发挥关键作用，而抗体多样性是维持完整黏膜屏障所必需的。
