Conventional T cell STAT3 and BATF are required for suppressing pathogenic gamma delta T cell responses during Inflammatory Bowel Disease 9019

Description Inflammatory bowel disease (IBD) is a spectrum of disorders characterized by distinct patterns of intestinal inflammation and a dysregulated intestinal immune response. Given the growing number of new diagnoses and the inconsistent results of current treatments, there is a major unmet need to understand IBD pathology to develop more effective therapies. The IBD-associated immune response is highly multi-faceted and consists of a network of adaptive T cells and innate-like γδ T cells that produce inflammatory cytokines and are associated with intestinal damage. Despite the association of these cell types with disease, how these responses become dysregulated and contribute to intestinal inflammation remains largely undefined. Here, I demonstrate that mice with conventional T cell-specific deletions in the transcription factors STAT3 and BATF develop spontaneous colitis marked by elevated numbers of microbiota-dependent inflammatory γδ T cells that mimic those found in human IBD. Further, γδ T cells are important for promoting disease as in vivo blockade of the γδ T cell receptor (TCR) reduces IBD-associated weight loss. Together, these data indicate that a STAT3/BATF+ conventional T cell population is critical for regulation of inflammatory γδ T cells and that therapeutic targeting of this adaptive/innate-like T cell interaction may be beneficial in preventing or treating IBD. Funding Sources Supported by NIH/NIDDK R21AI176326-02; NIH/NIDDK F31DK135369 Topic Categories Mucosal and Regional Immunology (MUC)