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J Exp Med. 2009 Jun 8;206(6):1365-78. doi: 10.1084/jem.20090127. Epub 2009 May 18.

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

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Institut National de la Santé et de la Recherche Médicale, U561/Groupe AVENIR, Hôpital Cochin St Vincent de Paul, Université Descartes, Paris F-75014, France.


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-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.

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