The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20090127
The Journal of Experimental Medicine, Vol. 206, No. 6, 1365-1378
The Rockefeller University Press, 0022-1007 $30.00
© Doisne et al.
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ARTICLE

 iNKT cell development is orchestrated by different branches of TGF-β signaling

Jean-Marc Doisne1, Laurent Bartholin2,6,7,9, Kai-Ping Yan4, Céline N. Garcia3,6,8, Nadia Duarte1, Jean-Benoît Le Luduec5,6, David Vincent2,6,7,9, Farhan Cyprian3,6,8, Branka Horvat3,6,8, Sylvie Martel2,6,7,9, Ruth Rimokh2,6,7, Régine Losson4, Kamel Benlagha1, and Julien C. Marie3,6,8

1 Institut National de la Santé et de la Recherche Médicale (INSERM), U561/Groupe AVENIR, Hôpital Cochin St Vincent de Paul, Université Descartes, Paris F-75014, France
2 INSERM, U590, IFR62, Lyon, F-69008, France
3 INSERM, U758, IFR128, Lyon, F-69007, France
4 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, F-67404, France
5 INSERM U851 IFR128, Lyon, F-69007, France
6 Université Lyon, Lyon, F-69003, France
7 Centre Léon Bérard, Lyon, F-69008, France
8 Ecole Normale Superieure de Lyon, Lyon, F-69007, France
9 INSERM, U590/Groupe AVENIR, Lyon, F-69008, France

CORRESPONDENCE Julien C. Marie: julien.marie{at}inserm.fr

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-β controls the differentiation program of iNKT cells. We demonstrate that TGF-β signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-β involves the concerted action of different pathways of TGF-β signaling. Whereas the Tif-1{gamma} branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1{gamma}/Smad4-independent branch. Thus, these three different branches of TGF-β signaling function in concert as complementary effectors, allowing TGF-β to fine tune the iNKT cell differentiation program.

K.-P. Yan's present address is The Wistar Institute, Philadelphia, PA 19104.

J.-M. Doisne and L. Bartholin contributed equally to this paper.

Abbreviations used: {alpha}GalCer, {alpha}-galactosylceramide; AAD, amino-actinomycin-D; CA, constitutively active; DP, double-positive; iNKT, invariant natural killer T; Tif-1{gamma}, transcriptional intermediary factor 1{gamma}.

© 2009 Doisne et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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