TY - JOUR
T1 - Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells
AU - Chen, Zhi
AU - Laurence, Arian
AU - Kanno, Yuka
AU - Pacher-Zavisin, Margit
AU - Zhu, Bing Mei
AU - Tato, Cristina
AU - Yoshimura, Akihiko
AU - Hennighausen, Lothar
AU - O'Shea, John J.
PY - 2006/5/23
Y1 - 2006/5/23
N2 - 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.
AB - 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.
KW - Signal transducer and activator of transcription 3
KW - T lymphocytes
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U2 - 10.1073/pnas.0600666103
DO - 10.1073/pnas.0600666103
M3 - Article
C2 - 16698929
AN - SCOPUS:33744479688
SN - 0027-8424
VL - 103
SP - 8137
EP - 8142
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -