Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells.
Suppressor of cytokine signaling (Socs) 3 is a cytokine-inducible inhibitor with critical but selective cell-specific effects. We show that deficiency of Socs3 in T cells had minimal effects on differentiation of T cells to the T helper (Th) 1 or Th2 subsets; accordingly, Socs3 had no effect on IL-12-dependent signal transducer and activator of transcription (Stat) 4 phosphorylation or IL-4-dependent Stat6 phosphorylation. By contrast, Socs3 was found to be a major regulator of IL-23-mediated Stat3 phosphorylation and Th17 generation, and Stat3 directly binds to the IL-17A and IL-17F promoters. We conclude that Socs3 is an essential negative regulator of IL-23 signaling, inhibition of which constrains the generation of Th17 differentiation.
Chen
Zhi
Z
Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Laurence
Arian
A
Kanno
Yuka
Y
Pacher-Zavisin
Margit
M
Zhu
Bing-Mei
BM
Tato
Cristina
C
Yoshimura
Akihiko
A
Hennighausen
Lothar
L
O'Shea
John J
JJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D002469:Cell Separation; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D050797:STAT4 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation
C508840:IL23A protein, human; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C106644:SOCS3 protein, human; D050797:STAT4 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins