Year: 2018
Type: article
Abstract: MicroRNAs have emerged as key regulators in T cell development, activation, and differentiation, with miR-181a having a prominent function. By targeting several signaling pathways, miR-181a is an important rheostat controlling T cell receptor (TCR) activation thresholds in thymic selection as well as peripheral T cell responses. A decline in miR-181a expression, due to reduced transcription of pri-miR-181a, accounts for T cell activation defects that occur with older age. Here we examine the transcriptional regulation of miR-181a expression and find a putative pri-miR-181a enhancer around position 198,904,300 on chromosome 1, which is regulated by a transcription factor complex including YY1. The decline in miR-181a expression correlates with reduced transcription of YY1 in older individuals. Partial silencing of YY1 in T cells from young individuals reproduces the signaling defects seen in older T cells. In conclusion, YY1 controls TCR signaling by upregulating miR-181a and dampening negative feedback loops mediated by miR-181a targets.
Source: Nature Communications
Authors: Zhongde Ye, Guangjin Li, Chulwoo Kim, Bin Hu, Rohit R. Jadhav, Cornelia M. Weyand, Jörg J. Goronzy
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1108740576, G1809139246, Influence of Age on CD4 T Memory Cells, G366100091, Oligoclonal T Cell Expansion and Rheumatoid Arthritis, G6241365711, G7126395394, Memory T Cell Development and Survival in T Cell Responses of Older Individuals, G8291144753, G8865692945, G9000017482, G9000051380, G9000060880, G9000107322, G9000110302, G9000123093, G9000126294, G9000137488, G9000150726, G9000222606, G9000269492, The NOTCH Signaling Pathway in Large Vessel Vasculitis, Vaccine and Infection Induced Immunity in the Young and Aged
OpenAlex ID: W2886871808