Blood Journal
Leading the way in experimental and clinical research in hematology

Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis

  1. Alexander Mildner1,
  2. Elik Chapnik2,
  3. Ohad Manor3,
  4. Simon Yona1,
  5. Ki-Wook Kim1,
  6. Tegest Aychek1,
  7. Diana Varol1,
  8. Gilad Beck2,
  9. Zohar Barnett Itzhaki1,
  10. Ester Feldmesser4,
  11. Ido Amit1,
  12. Eran Hornstein2, and
  13. Steffen Jung1
  1. Departments of 1Immunology,
  2. 2Molecular Genetics,
  3. 3Computer Science and Applied Mathematics, and
  4. 4Biological Services, Weizmann Institute of Science, Rehovot, Israel

Key Points

  • Ex vivo isolated myeloid populations of the mononuclear phagocyte network display specific microRNA expression signatures.

  • miR-142–deficient mice display a reduction of splenic CD4+ dendritic cells resulting in impaired priming of CD4 T-cell responses.

Abstract

The mononuclear phagocyte system comprises cells as diverse as monocytes, macrophages, and dendritic cells (DCs), which collectively play key roles in innate immune responses and the triggering of adaptive immunity. Recent studies have highlighted the role of growth and transcription factors in defining developmental pathways and lineage relations within this cellular compartment. However, contributions of miRNAs to the development of mononuclear phagocytes remain largely unknown. In the present study, we report a comprehensive map of miRNA expression profiles for distinct myeloid populations, including BM-resident progenitors, monocytes, and mature splenic DCs. Each of the analyzed cell populations displayed a distinctive miRNA profile, suggesting a role for miRNAs in defining myeloid cell identities. Focusing on DC development, we found miR-142 to be highly expressed in classic FLT3-L–dependent CD4+ DCs, whereas reduced expression was observed in closely related CD8α+ or CD4CD8α DCs. Moreover, mice deficient for miR-142 displayed an impairment of CD4+ DC homeostasis both in vitro and in vivo. Furthermore, loss of miR-142–dependent CD4+ DCs was accompanied by a severe and specific defect in the priming of CD4+ T cells. The results of our study establish a novel role for miRNAs in myeloid cell specification and define miR-142 as a pivotal genetic component in the maintenance of CD4+ DCs.

  • Submitted July 29, 2012.
  • Accepted October 23, 2012.
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