期刊
HUMAN IMMUNOLOGY
卷 77, 期 2, 页码 201-213出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2015.12.004
关键词
Suppressive cells; RNA sequencing; Gene signature; MiRNA; Differentially expressed; nCounter analysis; RTKN2; LAYN; FoxP3; MiR-146a; MiR-146b; MiR-21; PNA
类别
资金
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
The major goal of this study was to perform an in depth characterization of the gene signature of human FoxP3(+) T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro, were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3, IKZF2, and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes (RTKN2, LAYN, UTS2, CSF2RB, TRIB1, F5, CECAM4, CD70, ENC1 and NKG7) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs. Published by Elsevier on behalf of American Society for Histocompatibility and Immunogenetics. Inc.
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