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.

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Figure 1: Expression of microRNA describes and discriminates among different lymphocyte subsets.
Figure 2: Identification of putative miR-125b target genes in naive CD4+ T cells and description of their functional relationships.
Figure 3: Direct regulation by miR-125b of genes key to T cell differentiation.
Figure 4: Preservation of the naive state of CD4+ T cells by miR-125b.
Figure 5: Regulation of the differentiation of naive CD4+ T cells by miR-125b.

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Acknowledgements

We thank P. Dellabona, P. De Candia and S. Monticelli for discussions. Supported by the National Research Fund of Luxembourg (PDR-08-040 to L.W.) and the Fondazione Cariplo.

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R.L.R., G.R. and L.W. designed and did experiments, analyzed data and wrote the manuscript; M.M. and M.C.C. did flow cytometry; R.J.P.B. did bioinformatic analyses; M.C. did statistical analyses; R.S.B., S.C., S.M., P.G., F.M., D.M., V.P. and A.R. did experiments and analyzed data; E.T. provided advice; R.D.F. discussed results, provided advice and commented on the manuscript; J.G. designed and supervised research and wrote the manuscript; and S.A. and M.P. designed the study, supervised research and wrote the manuscript.

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Correspondence to Sergio Abrignani or Massimiliano Pagani.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Tables 1–4 and Supplementary Methods (PDF 1048 kb)

Supplementary Spreadsheet

RTqPCR raw CT data for all samples profiled. (TXT 218 kb)

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Rossi, R., Rossetti, G., Wenandy, L. et al. Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nat Immunol 12, 796–803 (2011). https://doi.org/10.1038/ni.2057

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