Kedar Batkulwar, Syed Bilal Ahmad Andrabi, Roosa Kattelus, Tanja Buchacher, Ilona Arnkil, Inna Starskaia, Omid Rasool, Robert Moulder, Riitta Lahesmaa
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引用次数: 0
Abstract
Regulatory T cells (Treg) play a central role in maintaining immune homeostasis, and the implementation of in vitro induced Treg cells (iTreg) to control immune function has significant potential in clinical medicine. The clinical application of iTreg has been limited by their poor stability. To better define the molecular characteristics of human iTreg, we performed a data-independent acquisition proteomics, detecting over 8000 proteins and providing a quantitative comparison of their relative levels in iTreg and activated Th0 cells. Consistent with the known molecular characteristics of Treg, several Treg signature proteins, including FOXP3, IKZF4, IL2RA, CTLA4, PD-1, IKZF3, LAG3, RUNX1 and hypermethylated in cancer 1, were identified and validated using Tier two targeted SRM and/or qRT-PCR. Notably, Leupaxin level was upregulated during Treg cell differentiation. Functional studies demonstrated that LPXN-deficient cells showed impaired expression of Treg protein markers FOXP3, IKZF4 and IKZF3 and impaired suppression of effector T cells. In addition, we identified a distinct CD160+ iTreg subpopulation characterized by a distinct proteomic signature as compared to CD160- iTreg. Together, these findings provide a high-resolution proteomic landscape of human iTreg and identified a novel role of LPXN in the development and suppressive activity of iTreg.
期刊介绍：
The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action.
The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data.
Scope:
-Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights
-Novel experimental and computational technologies
-Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes
-Pathway and network analyses of signaling that focus on the roles of post-translational modifications
-Studies of proteome dynamics and quality controls, and their roles in disease
-Studies of evolutionary processes effecting proteome dynamics, quality and regulation
-Chemical proteomics, including mechanisms of drug action
-Proteomics of the immune system and antigen presentation/recognition
-Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease
-Clinical and translational studies of human diseases
-Metabolomics to understand functional connections between genes, proteins and phenotypes
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