Transcription Factor RUNX3 Mediates Plasticity of ThGM Cells Toward Th1 Phenotype.

Abstract

GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that in addition to T-bet, TF RUNX3 also contributes to the Th1 switch of ThGM cells. T-bet-deficient ThGM cells in the CNS of mice with EAE had low expression of RUNX3, and knockdown of RUNX3 expression in ThGM cells abrogated the Th1-inducing effect of IL-12. Comparison of ThGM and Th1 cell transcriptomes showed that ThGM cells expressed a set of TFs known to inhibit the development of other Th lineages. Lack of expression of lineage-specific cytokines and TFs by ThGM cells, together with expression of TFs that inhibit the development of other Th lineages, suggests that ThGM cells are a non-polarized subset of Th cells with lineage characteristics.

• Authors: Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 912583 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35860266 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Rasouli, Casella, Zhang, Xiao, Kumar, Fortina, Zhang, Ciric and Rostami.

Chemical References

• Core Binding Factor Alpha 3 Subunit
• Cytokines
• Runx3 protein, mouse
• Transcription Factors
• Interleukin-12
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Core Binding Factor Alpha 3 Subunit (metabolism)
• Cytokines (metabolism)
• Encephalomyelitis, Autoimmune, Experimental
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Interleukin-12 (metabolism)
• Mice
• Multiple Sclerosis
• Phenotype
• Th1 Cells
• Th17 Cells
• Transcription Factors (metabolism)