Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment.
WSX-1 is a member of the class I cytokine receptor family with homology to IL-12R beta 2 and is essential for the initial mounting of Th1 responses. STAT1 interacts with tyrosine-phosphorylated WSX-1, and the conserved tyrosine residue of the cytoplasmic domain of WSX-1 is essential for transcriptional activation of STAT1. IL-27 stimulation induced STAT1 phosphorylation in wild-type but not in WSX-1-deficient naive CD4(+) T cells. Although IL-27 did not directly induce IFN-gamma production by wild-type CD4(+) T cells, IL-12-dependent IFN-gamma production was augmented by IL-27 stimulation in wild-type naive CD4(+) T cells but was impaired in WSX-1-deficient naive CD4(+) T cells. Additionally, IL-27 stimulation induced T-bet and IL-12R beta 2 expression in wild-type, but not in WSX-1-deficient, CD4(+) T cells. Thus, during the initiation of Th1 differentiation, the IL-27/WSX-1 signaling system plays a pivotal role by STAT1-mediated T-bet induction before the IL-12R system.
Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, and Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Atsunobu
A
Takeda
Shinjiro
S
Hamano
Atsushi
A
Yamanaka
Toshikatsu
T
Hanada
Tatsuro
T
Ishibashi
Tak W
TW
Mak
Akihiko
A
Yoshimura
Hiroki
H
Yoshida
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology; D007378:Interleukins / Q000502:physiology*; D053613:Janus Kinase 1; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation / Q000276:immunology*; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; C112441:IL27RA protein, human; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; C464565:MYDGF protein, human; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1