iNKT cell development is orchestrated by different branches of TGF-beta signaling.
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.
Doisne
Jean-Marc
JM
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.
Bartholin
Laurent
L
Yan
Kai-Ping
KP
Garcia
Céline N
CN
Duarte
Nadia
N
Le Luduec
Jean-Benoît
JB
Vincent
David
D
Cyprian
Farhan
F
Horvat
Branka
B
Martel
Sylvie
S
Rimokh
Ruth
R
Losson
Régine
R
Benlagha
Kamel
K
Marie
Julien C
JC
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D020825:T-Box Domain Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
D053646:Interleukin-2 Receptor beta Subunit; D018125:Receptors, Transforming Growth Factor beta; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C491420:Trim33 protein, mouse