Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

Abstract

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (T) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and Tcells was found within T cell zones of colonic lymphoid follicles. Tcells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted Tcell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, Tcells transdifferentiated into long-lived pathogenic T1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of Tcells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.