| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, H. San Raffaele Scientific Institute, Milan, Italy;
Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge, United Kingdom; and
Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London, U.K.
Invariant NK T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small noncoding RNAs that regulate gene expression posttranscriptionally and play a key role in the control of cellular differentiation programs. To this aim, we investigated iNKT cell development in mice in which Dicer, the RNase III enzyme that generates functional microRNAs, is deleted in cortical thymocytes. We find that Dicer deletion results in a substantial reduction of iNKT cells in thymus and their disappearance from the periphery, unlike mainstream T cells. Without Dicer, iNKT cells do not complete their innate effector differentiation and display a defective homeostasis due to increased cell death. Differentiation and homeostasis of iNKT cells require Dicer in a cell-autonomous fashion. Furthermore, we identify a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes, consistent with the idea that iNKT cells undergo agonist thymic selection. Together, these results define a critical role of the Dicer-dependent miRNA pathway in the physiology of iNKT cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by Associazione Italiana per la Ricerca sul Cancro, Fondazione Cariplo, Italian Ministry of Health (to P.D. and G.C.) and Biotechnology and Biological Sciences Research Council (to F.C.). M.F. is supported by fellowships from the PhD Program in Molecular Medicine, University of Vita-Salute San Raffaele (Milano, Italy).
2 Address correspondence and reprint requests to Dr. Paolo Dellabona or Giulia Casorati, Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, H. San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy. E-mail addresses: dellabona.paolo{at}hsr.it and casorati.giulia{at}hsr.it
3 Abbreviations used in this paper: iNKT, invariant NK T cell; DP, double positive; miRNA, microRNA; Treg, regulatory T cell; wt, wild type; SP, single positive; qRT-PCR, quantitative RT-PCR.
4 The online version of this article contains supplemental material.
Related articles in The JI:
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
