Elevation of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing T helper (TH) cells has been associated with several autoimmune diseases, suggesting a potential role in the pathogenesis of autoimmunity. However, the identity of GM-CSF-producing TH cells has not been closely examined. Using single-cell RNA sequencing and high-dimensional single-cell mass cytometry, we identified eight populations of antigen-experienced CD45RA-CD4+ T cells in blood of healthy individuals including a population of GM-CSF-producing cells, known as THGM, that lacked expression of signature transcription factors and cytokines of established TH lineages. Using GM-CSF-reporter/fate reporter mice, we show that THGM cells are present in the periphery and central nervous system in a mouse model of experimental autoimmune encephalomyelitis. In addition to GM-CSF, human and mouse THGM cells also expressed IL-2, tumor necrosis factor (TNF), IL-3, and CCL20. THGM cells maintained their phenotype through several cycles of activation but up-regulated expression of T-bet and interferon-γ (IFN-γ) upon exposure to IL-12 in vitro and in the central nervous system of mice with autoimmune neuroinflammation. Although T-bet was not required for the development of THGM cells, it was essential for their encephalitogenicity. These findings demonstrate that THGM cells constitute a distinct population of TH cells with lineage characteristics that are poised to adopt a TH1 phenotype and promote neuroinflammation.
A distinct GM-CSF+ T helper cell subset requires T-bet to adopt a TH1 phenotype and promote neuroinflammation / Rasouli, J.; Casella, G.; Yoshimura, S.; Zhang, W.; Xiao, D.; Garifallou, J.; Gonzalez, M. V.; Wiedeman, A.; Kus, A.; Mari, E. R.; Fortina, P.; Hakonarson, H.; Long, S. A.; Zhang, G. -X.; Ciric, B.; Rostami, A.. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 5:52(2020), p. eaba9953. [10.1126/sciimmunol.aba9953]