TY - JOUR
T1 - Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity
AU - Cuadrado, Eloy
AU - van den Biggelaar, Maartje
AU - de Kivit, Sander
AU - Chen, Yi-yen
AU - Slot, Manon
AU - Doubal, Ihsane
AU - Meijer, Alexander
AU - van Lier, Rene A. W.
AU - Borst, Jannie
AU - Amsen, Derk
PY - 2018
Y1 - 2018
N2 - 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. Using high-resolution mass spectrometry and transcriptomics, Cuadrado et al. provide a molecular characterization of regulatory and conventional CD4+ T cell subsets, yielding markers to distinguish cells with different properties and insights into mechanisms that prevent regulatory T cells from exhibiting undesirable functional activities of the related but functionally antithetical conventional T cells.
AB - 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. Using high-resolution mass spectrometry and transcriptomics, Cuadrado et al. provide a molecular characterization of regulatory and conventional CD4+ T cell subsets, yielding markers to distinguish cells with different properties and insights into mechanisms that prevent regulatory T cells from exhibiting undesirable functional activities of the related but functionally antithetical conventional T cells.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046777722&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29752063
U2 - https://doi.org/10.1016/j.immuni.2018.04.008
DO - https://doi.org/10.1016/j.immuni.2018.04.008
M3 - Article
C2 - 29752063
SN - 1074-7613
VL - 48
SP - 1046-1059.e6
JO - Immunity
JF - Immunity
IS - 5
ER -