The cytokine granulocyte
-macrophage colony
-stimulating factor (
GM-
CSF) is involved
in the pathogenesis of chronic inflammatory diseases such as multiple sclerosis. However, the environmental cues promoting
differentiation of
GM-
CSF producing
T cells are unclear. Herein, we performed a broad experimental screening of cytokines and data
-driven analysis assessing their ability to induce
human GM-
CSF+ CD4+ T cells and their subpopulations.
TGF-
β was discovered to induce
GM-
CSF production independently of proliferation and IL
-2 signaling including STAT5.
In contrast, IL
-6 and IL
-23 decreased
GM-
CSF production. On the population level,
GM-
CSF induction was highly correlated with expression of FOXP3 across cytokine stimulations but not with that of IL
-17. However, on single
-cell level
GM-
CSF and IFN
-γ expression were most correlated, independently of the cytokine environment. Importantly, under low
sodium conditions
in the medium or upon stimulation with plate
-bound instead of bead
-bound anti
-CD3 and anti
-CD28 antibodies,the effects of
TGF-
β on
GM-
CSF, but not on FOXP3, were reversed. Our analysis indicates a novel role for
TGF-
β in generating
GM-
CSF+ subsets of
human CD4+ T cells. These results are important for understanding of autoimmune disease and therapeutic considerations.
DOI: 10.3389/fimmu.2016.00603
TGF-β affects the differentiation of human GM-CSF+ CD4+ T cells.pdf