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Mol Cell Proteomics. 2017 Aug;16(8):1416-1432. doi: 10.1074/mcp.M116.062745. Epub 2017 Apr 3.

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

Author information

1
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.
2
§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.
3
¶UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 31000 Toulouse, France.
4
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.

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 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.

PMID:
28373295
PMCID:
PMC5546195
DOI:
10.1074/mcp.M116.062745
[Indexed for MEDLINE]
Free PMC Article

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