PT  - JOURNAL ARTICLE
AU  - Gilles Marodon
TI  - In silico characterization of a “universal” Treg signature reveals the proenkephalin gene as a novel Treg marker
AID  - 10.1101/638072
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 638072
4099  - http://biorxiv.org/content/early/2019/05/16/638072.short
4100  - http://biorxiv.org/content/early/2019/05/16/638072.full
AB  - Regulatory T cells (Treg) are crucial in the proper balance of the immune system. A better knowledge of Treg-specific genes may provide novel targets for therapeutic purposes and extend our knowledge on their complex biology. However, to date there is no consensual Treg signature in the literature. Here, we extracted a list of 72 genes differentially expressed in Treg compared to CD4+ conventional T cells across 6 different but comparable publicly available datasets. Most of the genes from this list did not connect to each other in a functional protein network analysis, but a third of those interacted somehow with IL-2, confirming the central role for this cytokine in Treg biology. When projected into a quantitative gene expression database, many genes of the Meta-Treg signature were also expressed by other immune and non-immune cell subsets, with the noticeable exceptions of Foxp3, Ctla4, Tnfrsf4 and Tnfrsf9 and surprisingly, the pro enkephalin (Penk) gene. Subsequent bioinformatic analysis of available datasets indicated the molecular mechanisms that could explain specific Penk expression in Treg. Altogether, our results show that the “universal” Treg signature concerns a very limited set of genes centered on the IL-2 family, members of the TNF receptor superfamily, and the endogenous opioid pathway.TregRegulatory T cellsTconvConventional T cellsTNFRSFTumor Necrosis Factor Receptor Super FamilyMTSMeta-Treg SignatureTFTranscription FactorsMENKMet-EnkephalinPPIProtein-Protein Interactions