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.
|Original language||English (US)|
|Journal||Frontiers in Immunology|
|State||Published - 2016|
Bibliographical noteFunding Information:
Sé was supported by Karolinska Institute's faculty funds for doctoral education (KID funding); AS was supported by a Marie Curie Intra European Fellowship within the seventh European Community Framework Programme, the Dr. Åke Olsson Foundation, KI Research Foundations, and the Center of Excellence for Research on Inflammation and Cardiovascular Disease (CERIC); JA was supported by the Swedish Cancer Society (213/771), the Swedish Heart-Lung Foundation (20140571), and Stiftelsen Olle Engqvist Byggmästare (2012/596); JT was supported by Vetenskapsrådet Medicine and Health (Dnr 2011-3264), Torsten Söderberg Foundation, FP7 STATegra, AFA Insurance, and Stockholm County Council. Publication of the article was supported by the OpenAIRE FP7 post-grant open access publishing funds.
© 2016 éliás, Schmidt, Kannan, Andersson and Tegnér.
- Autoimmune diseases
- Human CD4 T cells
- Multiple sclerosis
- Multivariate analysis
ASJC Scopus subject areas
- Immunology and Allergy