title: Vitamin A Impairs the Reprogramming of Tregs into IL-17-Producing Cells during Intestinal Inflammation.
abstract: Maintaining the identity of Foxp3(+) regulatory T cells (Tregs) is critical for controlling immune responses in the gut, where an imbalance between Tregs and T effector cells has been linked to inflammatory bowel disease. Accumulating evidence suggests that Tregs can convert into Th17 cells and acquire an inflammatory phenotype. In this study, we used an adoptive transfer model of Ag-specific T cells to study the contribution of different factors to the reprogramming of in vitro-generated Treg cells (iTreg) into IL-17-producing cells in a mouse model of gut inflammation in vivo. Our results show that intestinal inflammation induces the reprogramming of iTreg cells into IL-17-producing cells and that vitamin A restrains reprogramming in the gut. We also demonstrate that the presence of IL-2 during the in vitro generation of iTreg cells confers resistance to Th17 conversion but that IL-2 and retinoic acid (RA) cooperate to maintain Foxp3 expression following stimulation under Th17-polarizing conditions. Additionally, although IL-2 and RA differentially regulate the expression of different Treg cell suppressive markers, Treg cells generated under different polarizing conditions present similar suppressive capacity.
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Tejón
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Valeria
authors.initials: V
authors.lastname: Manríquez
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile ; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: De Calisto
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Flores-Santibáñez
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Yessia
authors.initials: Y
authors.lastname: Hidalgo
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Natalia
authors.initials: N
authors.lastname: Crisóstomo
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Dominique
authors.initials: D
authors.lastname: Fernández
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sauma
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: J Rodrigo
authors.initials: JR
authors.lastname: Mora
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile.
authors.forename: María R
authors.initials: MR
authors.lastname: Bono
authors.affiliation: Departamento de Biología, Facultad de Ciencias, Universidad de Chile, 7800024 Santiago, Chile ; Fundación Ciencia & Vida, 7780272 Santiago, Chile ; Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146 Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosemblatt
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D065150:Cellular Reprogramming / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage; D014801:Vitamin A / Q000008:administration & dosage*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007376:Interleukin-2; D014801:Vitamin A; D014212:Tretinoin