title: iNKT cell development is orchestrated by different branches of TGF-beta signaling.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Doisne
authors.forename: Laurent
authors.initials: L
authors.lastname: Bartholin
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Yan
authors.forename: Céline N
authors.initials: CN
authors.lastname: Garcia
authors.forename: Nadia
authors.initials: N
authors.lastname: Duarte
authors.forename: Jean-Benoît
authors.initials: JB
authors.lastname: Le Luduec
authors.forename: David
authors.initials: D
authors.lastname: Vincent
authors.forename: Farhan
authors.initials: F
authors.lastname: Cyprian
authors.forename: Branka
authors.initials: B
authors.lastname: Horvat
authors.forename: Sylvie
authors.initials: S
authors.lastname: Martel
authors.forename: Ruth
authors.initials: R
authors.lastname: Rimokh
authors.forename: Régine
authors.initials: R
authors.lastname: Losson
authors.forename: Kamel
authors.initials: K
authors.lastname: Benlagha
authors.forename: Julien C
authors.initials: JC
authors.lastname: Marie
mesh_terms: 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
chemical_list: 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