microRNA-142 guards against autoimmunity by controlling Treg cell homeostasis and function.

Journal Article (Journal Article)

Regulatory T (Treg) cells are critical in preventing aberrant immune responses. Posttranscriptional control of gene expression by microRNA (miRNA) has recently emerged as an essential genetic element for Treg cell function. Here, we report that mice with Treg cell-specific ablation of miR-142 (hereafter Foxp3CremiR-142fl/fl mice) developed a fatal systemic autoimmune disorder due to a breakdown in peripheral T-cell tolerance. Foxp3CremiR-142fl/fl mice displayed a significant decrease in the abundance and suppressive capacity of Treg cells. Expression profiling of miR-142-deficient Treg cells revealed an up-regulation of multiple genes in the interferon gamma (IFNγ) signaling network. We identified several of these IFNγ-associated genes as direct miR-142-3p targets and observed excessive IFNγ production and signaling in miR-142-deficient Treg cells. Ifng ablation rescued the Treg cell homeostatic defect and alleviated development of autoimmunity in Foxp3CremiR-142fl/fl mice. Thus, our findings implicate miR-142 as an indispensable regulator of Treg cell homeostasis that exerts its function by attenuating IFNγ responses.

Full Text

Duke Authors

Cited Authors

  • Wang, W-L; Ouyang, C; Graham, NM; Zhang, Y; Cassady, K; Reyes, EY; Xiong, M; Davis, AM; Tang, K; Zeng, D; Boldin, MP

Published Date

  • February 18, 2022

Published In

Volume / Issue

  • 20 / 2

Start / End Page

  • e3001552 -

PubMed ID

  • 35180231

Pubmed Central ID

  • PMC8893712

Electronic International Standard Serial Number (EISSN)

  • 1545-7885

International Standard Serial Number (ISSN)

  • 1544-9173

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.3001552

Language

  • eng