title: STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation.
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.
authors.affiliation: 1] Cancer Science Institute of Singapore, YLL School of Medicine, National University of Singapore, Singapore [2] Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Wanqiang
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Cancer Science Institute of Singapore, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Science Institute of Singapore, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Immunology Programme and Department of Microbiology, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: Pey Yng
authors.initials: PY
authors.lastname: Low
authors.affiliation: Immunology Programme and Department of Microbiology, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: David Michael
authors.initials: DM
authors.lastname: Kemeny
authors.affiliation: 1] Cancer Science Institute of Singapore, YLL School of Medicine, National University of Singapore, Singapore [2] Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Departments of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Moh
authors.affiliation: 1] Departments of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA [2] Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Immunology Programme and Department of Microbiology, YLL School of Medicine, National University of Singapore, Singapore.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Cancer Science Institute of Singapore, YLL School of Medicine, National University of Singapore, Singapore [2] Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore [3] Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore [4] Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Fu
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017353:Gene Deletion; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000276:immunology*; D015851:Interleukin-7 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050799:STAT5 Transcription Factor / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015851:Interleukin-7; D050799:STAT5 Transcription Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor