Research ArticleT CELLS

A distinct GM-CSF+ T helper cell subset requires T-bet to adopt a TH1 phenotype and promote neuroinflammation

See allHide authors and affiliations

Science Immunology  23 Oct 2020:
Vol. 5, Issue 52, eaba9953
DOI: 10.1126/sciimmunol.aba9953

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Poised for pathogenicity

Production of GM-CSF by T helper cells not only guides adaptive immune responses but also can contribute to the pathogenesis of autoimmune disease. Rasouli et al. used single-cell RNA sequencing, mass cytometry, and GM-CSF fate mapper mice to identify a distinct subset of T helper cells in humans and mice that specialize in sustained GM-CSF production but lack key phenotypic features of other T helper lineages. In a murine model of experimental autoimmune encephalomyelitis, these cells were poised to up-regulate IFN-γ within the central nervous system and promote development of encephalitis, processes that required the transcription factor T-bet. These results provide insight into the identity of GM-CSF–producing CD4 T cells and their function during autoimmune neuroinflammation.

Abstract

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 CD45RACD4+ 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.

View Full Text

Stay Connected to Science Immunology