title: Reverse plasticity: TGF-β and IL-6 induce Th1-to-Th17-cell transdifferentiation in the gut.
abstract: Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells. Thus, IFN-γ-producing Th1 effector cells specific for an intestinal microbial antigen were shown to acquire IL-17-producing capacities in the gut in a mouse model of colitis, and in response to TGF-β and IL-6 in vitro. TGF-β induced Runx1, and together with IL-6 was shown to render the ROR-γt and IL-17 promoters in Th1 cells accessible for Runx1 binding. In this commentary, we discuss how this unexpected plasticity of Th1 cells challenges our view on the generation of Th1/17 cells with the capacity to co-produce IL-17 and IFN-γ, and consider possible implications of this Th1-to-Th17-cell conversion for therapies of inflammatory bowel diseases and protective immune responses against intracellular pathogens.
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy. geginat@ingm.org.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Paroni
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.
authors.forename: Ilko
authors.initials: I
authors.lastname: Kastirr
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Larghi
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.|Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi, Milan, Italy.|DISCCO, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
mesh_terms: D000818:Animals; D000066670:Cell Plasticity; D054338:Cell Transdifferentiation; D006801:Humans; D007111:Immunity, Cellular; D007239:Infections / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism*; D007422:Intestines / Q000276:immunology*; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
keywords: Plasticity; Runx1; TGF-β; Th1; Th17