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- Title
TGF-β Affects the Differentiation of Human GM-CSF<sup>+</sup> CD4<sup>+</sup> T Cells in an Activation- and Sodium-Dependent Manner.
- Authors
Éliás, Szabolcs; Schmidt, Angelika; Kannan, Venkateshan; Andersson, John; Tegnér, Jesper
- Abstract
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 datadriven 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.
- Subjects
REJUVENESCENCE (Botany); PLANT cells &; tissues; CYTOPROTECTION; CELL physiology; EMBRYOLOGY
- Publication
Frontiers in Immunology, 2016, Vol 7, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2016.00603