title: STAT3 Activation Impairs the Stability of Th9 Cells.
abstract: Th9 cells regulate multiple immune responses, including immunity to pathogens and tumors, allergic inflammation, and autoimmunity. Despite ongoing research into Th9 development and function, little is known about the stability of the Th9 phenotype. In this study, we demonstrate that IL-9 production is progressively lost in Th9 cultures during several rounds of differentiation. The loss of IL-9 is not due to an outgrowth of cells that do not secrete IL-9, as purified IL-9 secretors demonstrate the same loss of IL-9 in subsequent rounds of differentiation. The loss of IL-9 production correlates with increases in phospho-STAT3 levels within the cell, as well as the production of IL-10. STAT3-deficient Th9 cells have increased IL-9 production that is maintained for longer in culture than IL-9 in control cultures. IL-10 is responsible for STAT3 activation during the first round of differentiation, and it contributes to instability in subsequent rounds of culture. Taken together, our results indicate that environmental cues dictate the instability of the Th9 phenotype, and they suggest approaches to enhance Th9 activity in beneficial immune responses.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Benjamin J
authors.identifier: 0000-0002-2729-1798
authors.initials: BJ
authors.lastname: Ulrich
authors.affiliation: Department of Biochemistry and Immunology, University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil; and.
authors.forename: Felipe Fortino
authors.initials: FF
authors.lastname: Verdan
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, United Kingdom.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; mkaplan2@iupui.edu olsonmr@iupui.edu.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Mark H
authors.identifier: 0000-0002-2923-8245
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; mkaplan2@iupui.edu olsonmr@iupui.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Olson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016906:Interleukin-9; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10