MicroRNA 10a marks regulatory T cells

TY - JOUR

T1 - MicroRNA 10a marks regulatory T cells

AU - Jeker, Lukas T

AU - Zhou, Xuyu

AU - Gershberg, Kseniya

AU - de Kouchkovsky, Dimitri

AU - Morar, Malika M

AU - Stadthagen, Gustavo

AU - Lund, Anders H.

AU - Bluestone, Jeffrey A

PY - 2012/5/18

Y1 - 2012/5/18

N2 - 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.

AB - 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.

KW - Animals

KW - Cells, Cultured

KW - Diabetes Mellitus, Type 1

KW - Gene Expression

KW - Mice

KW - Mice, Inbred NOD

KW - MicroRNAs

KW - T-Lymphocytes, Regulatory

KW - Transforming Growth Factor beta

KW - Tretinoin

U2 - 10.1371/journal.pone.0036684

DO - 10.1371/journal.pone.0036684

M3 - Journal article

C2 - 22629323

SN - 1932-6203

VL - 7

SP - e36684

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 5

ER -