Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b

Abstract

MicroRNAs are small noncoding RNAs that regulate gene expression post-transcriptionally. Here we applied microRNA profiling to 17 human lymphocyte subsets to identify microRNA signatures that were distinct among various subsets and different from those of mouse lymphocytes. One of the signature microRNAs of naive CD4+ T cells, miR-125b, regulated the expression of genes encoding molecules involved in T cell differentiation, including IFNG, IL2RB, IL10RA and PRDM1. The expression of synthetic miR-125b and lentiviral vectors encoding the precursor to miR-125b in naive lymphocytes inhibited differentiation to effector cells. Our data provide an 'atlas' of microRNA expression in human lymphocytes, define subset-specific signatures and their target genes and indicate that the naive state of T cells is enforced by microRNA.

MicroRNAs in the regulation of TLR and RIG-I pathways

“…44,45 In the past few years, accumulating evidence has shown that miRNAs affect mammalian immune cell differentiation, the outcome of immune responses to infection and the development of immunological diseases. [46][47][48][49][50][51] Therefore, it is not surprising that miRNAs are involved in TLR and RIG-I signaling in the innate immune system.…”

MiR-125 in normal and malignant hematopoiesis

“…MiR-125b was demonstrated to inhibit cell differentiation of granulocytes and monocytes in the myeloid lineage [27][28][29] and of PCs 30,31 and naïve T-cells 32 in the lymphoid lineage. MiR-125b, one of the signature miRNAs of naïve CD4 þ T-cells, was found to regulate a network of gene-encoding molecules involved in T-cell differentiation into effector cells, including IFNG, IL2RB, IL10RA and PRDM1.…”

“…[29][30][31][32] High expression of miR-125b is observed in germinal center (GC) centroblasts during human B-lineage differentiation. It is suggested that miR-125b is an inhibitor of premature plasma cell (PC) differentiation, as it targets the transcription factors B-lymphocyte-induced maturation protein-1 (BLIMP-1) and interferon regulatory protein-4 (IRF-4) 30,31 ( Figure 2).…”

“…It may also regulate T-lymphoid differentiation as it has recently been demonstrated to be expressed in human naïve T-cells and to target several T-cell differentiation genes. 32 In 32D mouse myeloid cells, miR-125b was shown to be induced by granulocyte colony-stimulating factor and to negatively regulate granulocyte colony-stimulating factor signaling. 27 Therefore, the block in myeloid differentiation 29 caused by miR-125b may be the result of a negative feedback loop in the granulocyte colony-stimulating factor pathway.…”

Distinct MicroRNA Expression Profile and Targeted Biological Pathways in Functional Myeloid-derived Suppressor Cells Induced by Δ9-Tetrahydrocannabinol in Vivo

“…Significant changes in miRNA expression have been observed during cell development and differentiation (8 -10). Genome-wide analysis of miRNA expression has been performed for various immune cell types such as mouse lymphocyte subsets (11) and human B and T lymphocytes (5,9,11). Moreover, unique miRNA expression profiles are known to be associated with immune cells or their differentiation states (10,12).…”