IL-27-Induced Type 1 Regulatory T-Cells Produce Oxysterols that Constrain IL-10 Production
| Autor: | Vigne , Solenne, Chalmin , Fanny, Duc , Donovan, Clottu , Aurélie S, Apetoh , Lionel, Lobaccaro , Jean-Marc A, Christen , Isabelle, Zhang , Juan, Pot , Caroline |
|---|---|
| Přispěvatelé: | Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Department of Pathology and Immunology [Geneva, Switzerland], Université de Genève = University of Geneva (UNIGE)-Geneva University Hospitals - HUG [Switzerland], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Novartis Institutes for BioMedical Research (NIBR), University of Geneva [Switzerland]-Geneva University Hospitals - HUG [Switzerland], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institutes for BioMedical Research, Novartis, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
type 1 regulatory T cells
Epstein–Barr virus-induced G-protein coupled receptor 2 (EBI2) Immunology autoimmunity immunometabolism nuclear hormone liver X receptor cholesterol 25-hydroxylase ddc:616.07 CD4+ T cells [ SDV.IMM ] Life Sciences [q-bio]/Immunology oxysterols [SDV.IMM]Life Sciences [q-bio]/Immunology lipids (amino acids peptides and proteins) Original Research |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, 2017, 8, pp.1184. ⟨10.3389/fimmu.2017.01184⟩ Frontiers in Immunology, Frontiers, 2017, 8, pp.1184. ⟨10.3389/fimmu.2017.01184⟩ Frontiers in Immunology, Frontiers, 2017, 8, pp.1184. 〈https://www.frontiersin.org/articles/10.3389/fimmu.2017.01184/full〉. 〈10.3389/fimmu.2017.01184〉 Frontiers in Immunology, Vol. 8 (2017) P. 1184 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.01184⟩ |
| Popis: | IF 6.429; International audience; The behaviors of lymphocytes, including CD4(+) T helper cells, are controlled on many levels by internal metabolic properties. Lipid metabolites have recently been ascribed a novel function as immune response modulators and perturbation of steroids pathways modulates inflammation and potentially promotes a variety of diseases. However, the impact of lipid metabolism on autoimmune disease development and lymphocyte biology is still largely unraveled. In this line, oxysterols, oxidized forms of cholesterol, have pleiotropic roles on the immune response aside from their involvements in lipid metabolism. The oxysterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC) regulate antiviral immunity and immune cell chemotaxis. However, their physiological effects on adaptive immune response in particular on various subset CD4(+) T lymphocytes are largely unknown. Here, we assessed oxysterol levels in subset of CD4(+) T cells and demonstrated that 25-OHC and transcript levels of its synthesizing enzyme, cholesterol 25-hydroxylase, were specifically increased in IL-27-induced type 1 regulatory T (TR1) cells. We further showed that 25-OHC acts as a negative regulator of TR1 cells in particular of IL-10 secretion via liver X receptor signaling. Not only do these findings unravel molecular mechanisms accounting for IL-27 signaling but also they highlight oxysterols as pro-inflammatory mediators that dampens regulatory T cell responses and thus unleash a pro-inflammatory response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|