Pathogenic TH17 cells utilize BHLHE40 to instruct myeloid cells during autoimmune neuroinflammation
TH17 cells are implicated in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). We previously reported that the transcription factor BHLHE40 marks cytokine-producing pathogenic TH cells during EAE, and that its expression in T cells is required for clinical disease. Here, using dual reporter mice, we show BHLHE40 expression within TH1/17 and ex-TH17 cells following EAE induction. Il17a-Cre-mediated deletion of BHLHE40 in TH cells led to less severe EAE with reduced TH cell cytokine production. Characterization of the leukocytes in the central nervous system during EAE by scRNA-sequencing identified differences in the infiltrating myeloid cells when BHLHE40 was present or absent in TH17 cells. Our studies highlight the importance of BHLHE40 in promoting TH17 cell encephalitogenicity and instructing myeloid cell responses during active EAE. Overall design: Live CD45+ cells from the central nervous system were FACS sorted from either naïve mice or immunized Bhlhe40fl/fl, Cd4-Cre+ Bhlhe40fl/fl, or Il17a-Cre+ Bhlhe40fl/fl mice 14 days post-EAE immunization for scRNA-seq.