Skip to main content
Article thumbnail
Location of Repository

STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation

By Wanqiang Sheng, Fan Yang, Yi Zhou, Henry Yang, Pey Yng Low, David Michael Kemeny, Patrick Tan, Akira Moh, Mark H. Kaplan, Yongliang Zhang and Xin-Yuan Fu

Abstract

T helper (TH)-cell subsets, such as TH1 and TH17, mediate inflammation in both peripheral tissues and central nervous system. Here we show that STAT5 is required for T helper-cell pathogenicity in autoimmune neuroinflammation but not in experimental colitis. Although STAT5 promotes regulatory T cell generation and immune suppression, loss of STAT5 in CD4+ T cells resulted in diminished development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Our results showed that loss of encephalitogenic activity of STAT5-deficient autoreactive CD4+ T cells was independent of IFN-γ or interleukin 17 (IL-17) production, but was due to the impaired expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), a crucial mediator of T-cell pathogenicity. We further showed that IL-7-activated STAT5 promotes the generation of GM-CSF-producing CD4+ T cells, which were preferentially able to induce more severe EAE than TH17 or TH1 cells. Consistent with GM-CSF-producing cells being a distinct subset of TH cells, the differentiation program of these cells was distinct from that of TH17 or TH1 cells. We further found that IL-3 was secreted in a similar pattern as GM-CSF in this subset of TH cells. In conclusion, the IL-7-STAT5 axis promotes the generation of GM-CSF/IL-3-producing TH cells. These cells display a distinct transcriptional profile and may represent a novel subset of T helper cells which we designate as TH-GM

Topics: Encephalomyelitis, Autoimmune, Experimental, immunology, Granulocyte-Macrophage Colony-Stimulating Factor, STAT5 Transcription Factor, T-Lymphocytes, Helper-Inducer
Publisher: Nature Publishing Group
Year: 2014
DOI identifier: 10.1038/cr.2014.154
OAI identifier: oai:scholarworks.iupui.edu:1805/8855
Provided by: IUPUIScholarWorks
Journal:

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.