BHLHE40 Mediates Cross-Talk between Pathogenic T(H)17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis

T(H)17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor basic helix-loop-helix family member e40 (BHLHE40) marks cytokine-producing pathogenic T(H) cells during EAE, and that its expression in T cells is required for clinical disease. In this study, using dual reporter mice, we show BHLHE40 expression within T(H)1/17 and ex-T(H)17 cells following EAE induction. Il17a-Cre–mediated deletion of BHLHE40 in T(H) cells led to less severe EAE with reduced T(H) cell cytokine production. Characterization of the leukocytes in the CNS during EAE by single-cell RNA sequencing identified differences in the infiltrating myeloid cells when BHLHE40 was present or absent in T(H)17 cells. Our studies highlight the importance of BHLHE40 in promoting T(H)17 cell encephalitogenicity and instructing myeloid cell responses during active EAE.