MicroRNA-22 controls interferon alpha production and erythroid maturation in response to infectious stress in mice

Exp Hematol. 2017 Dec;56:7-15. doi: 10.1016/j.exphem.2017.09.001. Epub 2017 Sep 11.


MicroRNA-22 (miR-22) is a highly conserved microRNA that can regulate cell proliferation, oncogenesis, and cell maturation, especially during stress. In hematopoietic stem cells (HSCs), miR-22 has been reported to be involved in the regulation of key self-renewal factors, including Tet2. Recent work demonstrates that miR-22 also participates in regulation of the interferon (IFN) response, and expression profiling studies suggest that it is variably expressed at different stages in erythroid differentiation. We thus hypothesized that miR-22 regulates maturation of erythroid progenitors during stress hematopoiesis through its interaction with IFN. We compared the blood and bone marrow of wild-type (WT) and miR-22-deficient mice at baseline and upon infectious challenge with systemic lymphochoriomeningitis (LCMV) virus. miR-22-deficient mice maintained platelet counts better than WT mice during infection, but they showed significantly reduced red blood cells and hemoglobin. Analysis of bone marrow progenitors demonstrated better overall survival and improved HSC homeostasis in infected miR-22-null mice compared with WT, which was attributable to a blunted IFN response to LCMV challenge in the miR-22-null mice. We found that miR-22 was expressed exclusively in stage II erythroid precursors and downregulated upon infection in WT mice. Our results indicate that miR-22 promotes the IFN response to viral infection and that it functions at baseline as a brake to slow erythroid differentiation and maintain adequate erythroid potential. Impaired regulation of erythrogenesis in the absence of miR-22 can lead to anemia during infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia / genetics
  • Anemia / metabolism*
  • Anemia / virology
  • Animals
  • Erythroid Precursor Cells / metabolism*
  • Erythroid Precursor Cells / pathology
  • Erythropoiesis*
  • Gene Expression Profiling
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / metabolism*
  • Lymphocytic choriomeningitis virus / genetics
  • Lymphocytic choriomeningitis virus / metabolism*
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Stress, Physiological*


  • Interferon-alpha
  • MicroRNAs
  • Mirn22 microRNA, mouse