Establishing mechanisms of Thetis cell-mediated microbiota tolerance 9146

Description Intestinal commensal microorganisms profoundly affect host physiology and disease, including but not limited to metabolism, immune and neuro-development, tumorigenesis, and cancer immunotherapy. Thus, the immune system is important in establishing a harmonious symbiotic relationship with the microbiota. Our lab recently identified a novel lineage of RORγt+ antigen-presenting cells (APCs) named Thetis cells (TCs) and demonstrated a critical role for a subset of TCs, TC IV, in regulating tolerance to the gut microbiota through the generation of peripheral Treg (pTreg) cells. How TCs selectively establish tolerance to the microbiota, given antigenic overlap with pathogenic microbes, remains a key unanswered question. To answer this question, we will i) establish the localization of TCs within tissues and lymph nodes (LNs), ii) identify cellular interacting partners of TCs and iii) determine the mechanism by which TCs acquire microbiota antigens. In our preliminary work, we show that TC IV are specifically enriched in gut-draining LNs compared to non-gut LNs, and that TCs are rare in intestinal tissues, suggesting that TCs are LN-resident cells. In addition, we found that TCs express receptors that allow binding of antigen-antibody complexes. Our future work will address the migratory nature of TCs and the role of antibody-mediated antigen capture in microbiota tolerance. Topic Categories Mucosal and Regional Immunology (MUC)