title: MicroRNAs are implicated in the suppression of CD4+CD25− conventional T cell proliferation by CD4+CD25+ regulatory T cells.
abstract: CD4+CD25+ regulatory T cells (Tregs) are critical for sustaining immunological homeostasis. CD4+CD25− conventional T cells (Tcons) are the progenitors of populations including Th1, Th2, Th17, Tfh, and Treg cells. Suppression of Tcons proliferation by Tregs requires cell–cell contact and/or is mediated by immunosuppressive soluble factors. However, upon receiving suppressive signals from Tregs, the exact molecular responses in Tcons remain elusive. Here, by using microRNA (miRNA) microarray preliminary screening and quantitative RT-PCR (qRT-PCR) validation, we showed that paralleled with the suppression of the Tcons proliferation, miR-146a was induced but miR-106b and miR-21 were reduced in Tcons upon receiving suppressive signals from Tregs. Moreover, our results showed that either increase of miR-146a or decrease of miR-106b and miR-21 by using miRNA mimics or inhibitors in Tcons significantly enhanced the suppression triggered by Tregs. However, decrease of miR-146a or increase of miR-106b and miR-21 in Tcons impaired the suppression triggered by Tregs. Collectively, our findings demonstrate the roles of miR-146a, miR-106b and miR-21 in Tcons in regulating Treg-triggered immune-suppression.
authors.affiliation: Department of Pathogen Biology & Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China
authors.forename: Sha
authors.initials: S
authors.lastname: Zhou
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Dong
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiajun
authors.initials: X
authors.lastname: Chen
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xian
authors.initials: X
authors.lastname: Song
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Chuan
authors.initials: C
authors.lastname: Sun
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D020869:Gene Expression Profiling; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II