Proteomic Analysis of Regulatory T Cells Reveals the Importance of Themis1 in the Control of Their Suppressive Function

• Published in: Molecular & cellular proteomics Vol. 16; no. 8; pp. 1416 - 1432
• Main Authors: Duguet, Fanny, Locard-Paulet, Marie, Marcellin, Marlène, Chaoui, Karima, Bernard, Isabelle, Andreoletti, Olivier, Lesourne, Renaud, Burlet-Schiltz, Odile, Gonzalez de Peredo, Anne, Saoudi, Abdelhadi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2017; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology
• Subjects: Adaptive immunology; Animal biology; Animals; Cell lineage; Chromatography, Liquid; Cytometry; Disease Models, Animal; Flow Cytometry; Homeostasis; Human health and pathology; Humans; Immune Tolerance; Immunological diseases; Immunology; Immunoregulation; Inflammatory bowel diseases; Inflammatory Bowel Diseases - immunology; Intercellular Signaling Peptides and Proteins; Intestine; Life Sciences; Lymphocytes; Lymphocytes T; Mass spectrometry; Mass spectroscopy; Mathematical models; Mice; Mice, Inbred C57BL; Pathogenesis; Proteins; Proteins - analysis; Proteins - genetics; Proteins - metabolism; Proteomics - methods; Rodents; Subpopulations; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Tandem Mass Spectrometry; Transgenic mice
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M116.062745

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 Treg versus Tconv. 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 provided in vivo and in vitro evidence 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 activity in vitro is 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.