The P2X7 receptor (P2X7R) is a widely distributed cation channel activated by extracellular ATP (eATP) with exclusive peculiarities with respect to other P2XRs. In recent years, P2X7R has been shown to regulate the adaptive immune response by conditioning T cell signaling and activation as well as polarization, lineage stability, cell death, and function in tissues. Here we revise experimental observations in this field, with a focus on adaptive immunity at mucosal sites, particularly in the gut, where eATP is hypothesized to act in the reciprocal conditioning of the host immune system and commensal microbiota to promote mutualism. The importance of P2X7R activity in the intestine is consistent with the transcriptional upregulation of P2xr7 gene by retinoic acid, a metabolite playing a key role in mucosal immunity. We emphasize the function of the eATP/P2X7R axis in controlling T follicular helper (Tfh) cell in the gut-associated lymphoid tissue (GALT) and, consequently, T-dependent secretory IgA (SIgA), with a focus on high-affinity SIgA-mediated protection from enteropathogens and shaping of a beneficial microbiota for the host.

P2X7 受体 （P2X7R） 是一种由细胞外 ATP （eATP） 激活的广泛分布的阳离子通道，与其他 P2XR 相比具有独特的特性。近年来，P2X7R 已被证明通过调节 T 细胞信号传导和激活以及组织中的极化、谱系稳定性、细胞死亡和功能来调节适应性免疫反应。在这里，我们修改了该领域的实验观察结果，重点是粘膜部位的适应性免疫，特别是在肠道中，假设 eATP 在宿主免疫系统和共生微生物群的相互调节中发挥作用，以促进共生。P2X7R 活性在肠道中的重要性与视黄酸对 P2xr7 基因的转录上调一致，视黄酸是一种在粘膜免疫中起关键作用的代谢物。我们强调 eATP/P2X7R 轴在控制肠道相关淋巴组织 （GALT） 中的 T 滤泡辅助性 （Tfh） 细胞的功能，因此，T 依赖性分泌型 IgA （SIgA） 的作用，重点是高亲和力 SIgA 介导的对肠道病原体的保护作用和塑造对宿主有益的微生物群。