Reciprocal Regulation of T Follicular Helper Cells and Dendritic Cells Drives Chronic Colitis Development

Abstract The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (Tfh) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature type 2 conventional dendritic cells (cDC2s) and Tfh cells were found within T cell zones of colonic lymphoid follicles. Tfh cells were required for mature cDC2 accumulation, the formation of DC-T cell clusters and colitis development. Moreover, cDC2s promoted Tfh cell differentiation, contributing to colitis development. Importantly, a lineage-tracing analysis showed that, following migration to lamina propria, Tfh cells trans-differentiated into long-lived pathogenic Th1 cells. Our findings have therefore demonstrated the reciprocal regulation of Tfh cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.