Microbial modulation of intestinal T helper cell responses and implications for disease and therapy

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.