The MicroRNA miR-191 Supports T Cell Survival Following Common γ Chain Signaling.
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.
Duke Scholars
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Related Subject Headings
- Up-Regulation
- Signal Transduction
- Receptors, Antigen, T-Cell
- NIH 3T3 Cells
- MicroRNAs
- Mice, Inbred C57BL
- Mice
- Interleukin Receptor Common gamma Subunit
- Insulin Receptor Substrate Proteins
- Gene Deletion
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Up-Regulation
- Signal Transduction
- Receptors, Antigen, T-Cell
- NIH 3T3 Cells
- MicroRNAs
- Mice, Inbred C57BL
- Mice
- Interleukin Receptor Common gamma Subunit
- Insulin Receptor Substrate Proteins
- Gene Deletion