A distinct GM-CSF+ T helper cell subset requires T-bet to adopt a TH1 phenotype and promote neuroinflammation.
Sci Immunol
; 5(52)2020 Oct 23.
Article
in En
| MEDLINE
| ID: mdl-33097590
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-CSFproducing 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-CSFproducing 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Granulocyte-Macrophage Colony-Stimulating Factor
/
Th1 Cells
/
T-Box Domain Proteins
/
Encephalomyelitis, Autoimmune, Experimental
/
Multiple Sclerosis
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Sci Immunol
Year:
2020
Document type:
Article
Affiliation country:
United States