Loss of microRNAs in thymus perturbs invariant NKT cell development and function

Kook Heon Seo, Li Zhou, Dongmei Meng, Jianrui Xu, Zheng Dong, Qing Sheng Mi

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

microRNAs (miRNAs) are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level. Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development, including autoimmune diseases. Invariant natural killer T (iNKT) cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses. Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells. In the present study, to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development, we generated a mouse model with the Dicer deletion in the thymus. Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs. miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon ±-galactosylceramide (±-GalCer) stimulation. Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalCellular and Molecular Immunology
Volume7
Issue number6
DOIs
StatePublished - Nov 2010

Keywords

  • autoimmunity
  • development
  • iNKT cells
  • microRNAs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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