Induction of intestinal T helper cell subsets by commensal members of the intestinal microbiota is an important component of the many immune adaptations required to establish host-microbial homeostasis. Importantly, altered intestinal T helper cell profiles can have pathological consequences that are not limited to intestinal sites. Therefore, microbial-mediated modulation of the intestinal T helper cell profile could have strong therapeutic potentials. However, in order to develop microbial therapies that specifically induce the desired alterations in the intestinal T helper cell compartment one has to first gain a detailed understanding of how microbial composition and the metabolites derived or induced by the microbiota impact on intestinal T helper cell responses. Here we summarize the milestone findings in the field of microbiota-intestinal T helper cell crosstalk with a focus on the role of specific commensal bacteria and their metabolites. We discuss mechanistic mouse studies and are linking these to human studies where possible. Moreover, we highlight recent advances in the field of microbial CD4 T cell epitope mimicry in autoimmune diseases and the role of microbially-induced CD4 T cells in cancer immune checkpoint blockade therapy.

肠道微生物群的共生成员诱导肠道 T 辅助细胞亚群是建立宿主-微生物稳态所需的许多免疫适应的重要组成部分。重要的是，改变的肠道 T 辅助细胞谱可能会产生不限于肠道部位的病理后果。因此，微生物介导的肠道 T 辅助细胞谱的调节可能具有强大的治疗潜力。然而，为了开发特异性诱导肠道 T 辅助细胞区室所需改变的微生物疗法，必须首先详细了解微生物组成和微生物群衍生或诱导的代谢物如何影响肠道 T 辅助细胞反应。在这里，我们总结了微生物群-肠道 T 辅助细胞串扰领域的里程碑发现，重点关注特定共生细菌及其代谢物的作用。我们讨论机械小鼠研究，并在可能的情况下将这些研究与人类研究联系起来。此外，我们强调了自身免疫性疾病中微生物 CD4 T 细胞表位模拟领域的最新进展，以及微生物诱导的 CD4 T 细胞在癌症免疫检查点阻断疗法中的作用。