title: Proteomic Analysis of Regulatory T Cells Reveals the Importance of Themis1 in the Control of Their Suppressive Function.
abstract: Regulatory T cells (Treg) represent a minor subpopulation of T lymphocytes that is crucial for the maintenance of immune homeostasis. Here, we present a large-scale quantitative mass spectrometry study that defines a specific proteomic "signature" of Treg. Treg and conventional T lymphocyte (Tconv) subpopulations were sorted by flow cytometry and subjected to global proteomic analysis by single-run nanoLC-MS/MS on a fast-sequencing Q-Exactive mass spectrometer. Besides "historical" proteins that characterize Treg, our study identified numerous new proteins that are up- or downregulated in TregversusTconv. We focused on Themis1, a protein particularly under-represented in Treg, and recently described as being involved in the pathogenesis of immune diseases. Using a transgenic mouse model overexpressing Themis1, we providedin vivoandin vitroevidence of its importance for Treg suppressive functions, in an animal model of inflammatory bowel disease and in coculture assays. We showed that this enhanced suppressive activityin vitrois associated with an accumulation of Tregs. Thus, our study highlights the usefulness of label free quantitative methods to better characterize the Treg cell lineage and demonstrates the potential role of Themis1 in the suppressive functions of these cells.
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.|§Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024, Toulouse, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Duguet
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Locard-Paulet
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Marcellin
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Chaoui
authors.affiliation: §Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024, Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bernard
authors.affiliation: ¶UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 31000 Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andreoletti
authors.affiliation: §Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024, Toulouse, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Lesourne
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: From the ‡Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; Université de Toulouse, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, 31077 Toulouse, France; gonzalez@ipbs.fre-mail.
authors.forename: Anne
authors.initials: A
authors.lastname: Gonzalez de Peredo
authors.affiliation: §Centre de Physiopathologie de Toulouse Purpan, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, UPS, 31024, Toulouse, France.
authors.forename: Abdelhadi
authors.initials: A
authors.lastname: Saoudi
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D053719:Tandem Mass Spectrometry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C544192:themis protein, mouse