Abstract
MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a expression in vitro leads to reduced FoxP3 expression levels and miR-10a expression is lower in unstable "exFoxP3" T cells. Unstable in vitro TGF-ß-induced, iTregs do not express miR-10a unless cultured in the presence of retinoic acid (RA) which has been associated with increased stability of iTreg, suggesting that miR-10a might play a role in stabilizing Treg. However, genetic ablation of miR-10a neither affected the number and phenotype of natural Treg nor the capacity of conventional T cells to induce FoxP3 in response to TGFβ, RA, or a combination of the two. Thus, miR-10a is selectively expressed in Treg but inhibition by antagomiRs or genetic ablation resulted in discordant effects on FoxP3.
| Original language | English |
|---|---|
| Journal | PLOS ONE |
| Volume | 7 |
| Issue number | 5 |
| Pages (from-to) | e36684 |
| ISSN | 1932-6203 |
| DOIs | |
| Publication status | Published - 18 May 2012 |
Keywords
- Animals
- Cells, Cultured
- Diabetes Mellitus, Type 1
- Gene Expression
- Mice
- Mice, Inbred NOD
- MicroRNAs
- T-Lymphocytes, Regulatory
- Transforming Growth Factor beta
- Tretinoin
