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

Cellular & Molecular Immunology volume 7, pages 447–453 (2010)Cite this article

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 α-galactosylceramide (α-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.

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Acknowledgements

We thank M. McManus for Dicer-loxP mice, R. Qi for assistance with artwork and the NIH Tetramer Facility for CD1d tetramer. This work was support by grants from Juvenile Diabetes Research Foundation International (1-2005-1039, 5-2006-688 and 5-2006-918) and American Diabetes Association (7-05-JF-30).

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Authors and Affiliations

  1. Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, USA

    Kook-Heon Seo, Li Zhou & Qing-Sheng Mi

  2. Department of Dermatology, Henry Ford Health System, Detroit, MI, USA

    Kook-Heon Seo, Li Zhou & Qing-Sheng Mi

  3. Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA

    Li Zhou & Qing-Sheng Mi

  4. Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA, USA

    Dongmei Meng & Jianrui Xu

  5. Department of Internal Medicine, the Affiliated Hospital of Qingdao University Medical College, Qingdao, China

    Dongmei Meng

  6. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA, USA

    Zhong Dong

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  1. Kook-Heon Seo
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Correspondence to Li Zhou or Qing-Sheng Mi.

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Seo, KH., Zhou, L., Meng, D. et al. Loss of microRNAs in thymus perturbs invariant NKT cell development and function. Cell Mol Immunol 7, 447–453 (2010). https://doi.org/10.1038/cmi.2010.49

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