Summary Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal host defense against many invading pathogens. Commensal bacteria, especially segmented filamentous bacteria (SFB), are a crucial factor that drives T helper 17 (Th17) cell development in the gastrointestinal tract. In this study, we demonstrate that Th17 cells controlled SFB burden. Disruption of IL-17R signaling in the enteric epithelium resulted in SFB dysbiosis due to reduced expression of α-defensins, Pigr and Nox1. When subjected to experimental autoimmune encephalomyelitis, IL-17R signaling deficient mice demonstrated earlier disease onset and worsened severity that was associated with increased intestinal Csf2 expression and elevated systemic GM-CSF cytokine concentrations. Conditional deletion of IL-17R in the enteric epithelium demonstrated that there was a reciprocal relationship between the gut microbiota and enteric IL-17R signaling that controlled dysbiosis, constrained Th17 development, and regulated the susceptibility to autoimmune inflammation.

Innate immunity is maintained in part by antigen presenting cells (APCs) including dendritic cells, macrophages, and B cells. APCs interact with T cells to link innate and adaptive immune responses. By displaying bacterial and tumorigenic antigens on their surface via major histocompatibility complexes, APCs can directly influence the differentiation of T cells. Likewise, T cell activation, differentiation, and effector functions are modulated by APCs utilizing multiple mechanisms. The objective of this review is to describe how APCs interact with and influence the activation of T cells to maintain innate immunity during exposure to microbial infection and malignant cells. How bacteria and cancer cells take advantage of some of these interactions for their own benefit will also be discussed. While this review will cover a broad range of topics, a general focus will be held around pathogens, cancers, and interactions that typically occur within the gastrointestinal tract.

Significance Commensal microbiota are known to be required for the elicitation of host Th17 responses, which may mediate autoimmune diseases. Here, we demonstrate that the IL-23 pathway dynamically regulates the abundance of certain commensals and maintains barrier function. Barrier disruption results in systemic dissemination of microbial products, which invokes the IL-23 pathway, with both beneficial and potentially deleterious consequences. Through induction of IL-22, IL-23 contributes to barrier repair, and through induction of the Th17 response, it aims to neutralize escaped commensal microbes. Thus, barrier disruption results in a pro-Th17 environment in which not only antimicrobial but also potentially antihost Th17 cells can develop.