The MicroRNA miR-191 Supports T Cell Survival Following Common γ Chain Signaling.
Journal Article (Journal Article)
To ensure lifelong immunocompetency, naïve and memory T cells must be adequately maintained in the peripheral lymphoid tissues. Homeostatic maintenance of T cells is controlled by tonic signaling through T cell antigen receptors and common γ chain cytokine receptors. In this study, we identify the highly expressed microRNA miR-191 as a key regulator of naïve, memory, and regulatory T cell homeostasis. Conditional deletion of miR-191 using LckCre resulted in preferential loss of peripheral CD4+ regulatory T cells as well as naïve and memory CD8+ T cells. This preferential loss stemmed from reduced survival following deficient cytokine signaling and STAT5 activation. Mechanistically, insulin receptor substrate 1 (Irs1) is a direct target of miR-191, and dysregulated IRS1 expression antagonizes STAT5 activation. Our study identifies a novel role for microRNAs in fine-tuning immune homeostasis and thereby maintaining the lymphocyte reservoir necessary to mount productive immune responses.
- Lykken, EA; Li, Q-J
- November 4, 2016
Volume / Issue
- 291 / 45
Start / End Page
- 23532 - 23544
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States