Dataset Information


Quantitative Proteomics Reveals Specialized Wiring of Signaling Pathways that Protects Human Regulatory T Cell Identity - 5 populations ex vivo

ABSTRACT: Regulatory CD4+ T cells (Tregs) are functionally distinct from conventional CD4+ T cells (Tconvs). To understand Treg identity, we compared by proteomics and transcriptomics human naïve (n) and effector (e)Tregs, Tconvs and transitional FOXP3+ cells. Only 12% of 422 differentially expressed proteins was identified as such at the mRNA level, demonstrating the importance of direct proteome measurement. Fifty-one proteins discriminated Tregs from Tconvs. This common Treg protein signature indicates altered signaling by TCR-, TNF receptor-, NFB-, PI3 kinase/mTOR-, NFAT- and STAT pathways, and unique cell biological and metabolic features. Another protein signature uniquely identified eTregs and revealed active cell division, apoptosis sensitivity and suppression of NFB- and STAT signaling. eTreg fate appears consolidated by FOXP3 outnumbering its partner transcription factors. These features explain why eTregs cannot produce inflammatory cytokines, whereas transitional FOXP3+ cells can. Collectively, our data reveal that Treg identity is defined and protected by uniquely “wired” signaling pathways.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo sapiens  

TISSUE(S): Blood

DISEASE(S): Not Available

SUBMITTER: Maartje van den Biggelaar  

LAB HEAD: Dr. Maartje van den Biggelaar

PROVIDER: PXD005477 | Pride | 2018-05-18


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

Cuadrado Eloy E   van den Biggelaar Maartje M   de Kivit Sander S   Chen Yi-Yen YY   Slot Manon M   Doubal Ihsane I   Meijer Alexander A   van Lier Rene A W RAW   Borst Jannie J   Amsen Derk D  

Immunity 20180508 5

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 adaptation  ...[more]

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