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

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

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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 T H 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 T H cells. These cells display a distinct transcriptional profile and may represent a novel subset of T helper cells which we designate as TH-GM.

Original languageEnglish (US)
Pages (from-to)1387-1402
Number of pages16
JournalCell Research
Volume24
Issue number12
DOIs
StatePublished - Dec 11 2014

Keywords

  • experimental autoimmune encephalomyelitis
  • GM-CSF
  • IL-7
  • STAT5
  • T helper cell

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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