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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Differentiation / immunology*
  • Cell Lineage
  • Interleukin-2 Receptor beta Subunit / immunology
  • Mice
  • Mice, Transgenic
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / physiology*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / immunology
  • Signal Transduction / physiology*
  • Smad4 Protein / genetics
  • Smad4 Protein / immunology
  • Spleen / cytology
  • Stem Cells / cytology
  • Stem Cells / physiology
  • T-Box Domain Proteins / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*


  • Interleukin-2 Receptor beta Subunit
  • Receptors, Transforming Growth Factor beta
  • Smad4 Protein
  • Smad4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Transforming Growth Factor beta
  • Trim33 protein, mouse