MyD88 Signaling in T Cells Directs IgA-Mediated Control of the Microbiota to Promote Health

Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis. [Display omitted] •T cell-intrinsic MyD88 signaling promotes germinal center responses in the gut•Defects to this pathway disrupt homeostatic humoral responses against the microbiota•Abnormal humoral response alters IgA-mediated bias on microbiota composition•Altered microbiota enhances inflammatory disease Kubinak and Petersen et al. demonstrate that innate (MyD88-dependent) signaling in T cells coordinates homeostatic IgA-directed targeting against commensal microbes by promoting germinal center responses. Loss of this pathway results in abnormal IgA antibody responses and an altered microbial gut community that leads to more severe inflammatory disease.