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Immunity. 2018 May 15;48(5):1046-1059.e6. doi: 10.1016/j.immuni.2018.04.008. Epub 2018 May 8.

Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity.

Author information

1
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: eloycua@gmail.com.
2
Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
3
Division of Tumor Biology and Immunology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, 1066 CX Amsterdam, the Netherlands.
4
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
5
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: d.amsen@sanquin.nl.

Abstract

To obtain a molecular definition of regulatory T (Treg) cell identity, we performed proteomics and transcriptomics on various populations of human regulatory and conventional CD4+ T (Tconv) cells. A protein expression signature was identified that defines all Treg cells, and another signature that defines effector Treg cells. These signatures could not be extrapolated from transcriptome data. Unique cell-biological and metabolic features in Treg cells were defined, as well as specific adaptations in cytokine, TCR, and costimulatory receptor signaling pathways. One such adaptation-selective STAT4 deficiency-prevented destabilization of Treg cell identity and function by inflammatory cytokines, while these signals could still induce critical transcription factors and homing receptors via other pathways. Furthermore, our study revealed surface markers that identify FOXP3+CD4+ T cells with distinct functional properties. Our findings suggest that adaptation in signaling pathways protect Treg cell identity and present a resource for further research into Treg cell biology.

KEYWORDS:

FOXP3; NFAT; STAT4; proteomics; regulatory T cells; signal transduction; transcription factors; transcriptomics

PMID:
29752063
DOI:
10.1016/j.immuni.2018.04.008
[Indexed for MEDLINE]
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