流式细胞术
生物
免疫系统
质量细胞仪
细胞生物学
转基因
功能(生物学)
免疫学
体内
淋巴细胞
计算生物学
表型
基因
遗传学
作者
Fanny Duguet,Marie Locard‐Paulet,Marlène Marcellin,Karima Chaoui,Isabelle Bernard,Olivier Andréoletti,Renaud Lesourne,Odile Burlet‐Schiltz,Anne Gonzalez de Peredo,Abdelhadi Saoudi
标识
DOI:10.1074/mcp.m116.062745
摘要
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.
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