biostudies-literatureCook MENCATS NIH HHSNIAID NIH HHSNCI NIH HHS737-746https://www.ebi.ac.uk/biostudies/studies/S-EPMC10695412biostudies-literatureUnknown7(11)TH17 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 TH 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 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 CNS during EAE by single-cell RNA 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.ImmunoHorizonsBHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis.PMC10695412R01 AI132653P30 CA091842T32 AI007163UL1 TR002345R01 AI113118Schwarzkopf EAJarjour NNShchukina ILin CCCook MEWebber AMZaitsev KArtyomov MNEdelson BTBradstreet TRfalseBHLHE40 Mediates Cross-Talk between Pathogenic TH17 Cells and Myeloid Cells during Experimental Autoimmune Encephalomyelitis.TH17 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 TH 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 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 CNS during EAE by single-cell RNA 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.2023-01-01T00:00:00Z2023 Nov2026-05-29T07:38:20.776Z2025-02-19T01:18:07.122ZS-EPMC106954123793406010.4049/immunohorizons.2300042