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Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in T(h)1 and T(h)2 cells

Anderson, Per LU ; Sundstedt, A; Li, Li LU ; O'Neill, EJ; Li, Su-Ling LU ; Wraith, DC and Wang, P (2003) In International Immunology 15(11). p.1309-1317
Abstract
Cytokines direct the differentiation of naive CD4(+) T cells into either IFN-gamma-producing T(h)1 cells or IL-4-producing T(h)2 cells. In this study, we analyzed the activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT5 (together with STAT4 and STAT6), and the expression of the recently identified suppressor of cytokine signalling (SOCS) proteins, in differentiated T(h)1 and T(h)2 cells, both before and after re-stimulation with anti-CD3 and anti-CD28. In addition to the polarized activation of STAT4 in T(h)1 cells and STAT6 in T(h)2 cells, we found that STAT3 and STAT5 are selectively activated in T(h)1 cells after differentiation. This activation of STAT3 and STAT5 was maintained after TCR... (More)
Cytokines direct the differentiation of naive CD4(+) T cells into either IFN-gamma-producing T(h)1 cells or IL-4-producing T(h)2 cells. In this study, we analyzed the activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT5 (together with STAT4 and STAT6), and the expression of the recently identified suppressor of cytokine signalling (SOCS) proteins, in differentiated T(h)1 and T(h)2 cells, both before and after re-stimulation with anti-CD3 and anti-CD28. In addition to the polarized activation of STAT4 in T(h)1 cells and STAT6 in T(h)2 cells, we found that STAT3 and STAT5 are selectively activated in T(h)1 cells after differentiation. This activation of STAT3 and STAT5 was maintained after TCR re-stimulation. The selective activation of STAT3 and STAT5 in T(h)1 cells was associated with differential induction of SOCS molecules. After restimulation, SOCS1 expression was significantly increased in T(h)2 cells, but not in T(h)1 and nonpolarized 'T-h' cells. Additionally, the level of CIS was higher in T(h)2 cells compared with T(h)1 and T-h cells. In contrast, the expression of SOCS3 was higher in T(h)1 cells. The differential induction of SOCS proteins was paralleled by the differential expression of cytokines in re-stimulated T(h)1 and T(h)2 cells (IFN-gamma and IL-4/IL-13 respectively). Our results suggests that STAT3 and STAT5, possibly regulated by the SOCS proteins, may play a role in the differentiation of T-h cells, and in the maintenance of the T(h)1 and T(h)2 phenotype. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cytokine signalling, signal transducer and activator of transcription, suppressor of, T-h
in
International Immunology
volume
15
issue
11
pages
1309 - 1317
publisher
Oxford University Press
external identifiers
  • pmid:14565929
  • wos:000186325600005
  • scopus:0242636426
ISSN
1460-2377
DOI
10.1093/intimm/dxg130
language
English
LU publication?
yes
id
b60554a6-ec1b-451a-8b6f-4865372e2e7a (old id 296477)
alternative location
http://intimm.oxfordjournals.org/cgi/content/abstract/15/11/1309
date added to LUP
2007-08-22 10:52:18
date last changed
2018-05-29 11:21:26
@article{b60554a6-ec1b-451a-8b6f-4865372e2e7a,
  abstract     = {Cytokines direct the differentiation of naive CD4(+) T cells into either IFN-gamma-producing T(h)1 cells or IL-4-producing T(h)2 cells. In this study, we analyzed the activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT5 (together with STAT4 and STAT6), and the expression of the recently identified suppressor of cytokine signalling (SOCS) proteins, in differentiated T(h)1 and T(h)2 cells, both before and after re-stimulation with anti-CD3 and anti-CD28. In addition to the polarized activation of STAT4 in T(h)1 cells and STAT6 in T(h)2 cells, we found that STAT3 and STAT5 are selectively activated in T(h)1 cells after differentiation. This activation of STAT3 and STAT5 was maintained after TCR re-stimulation. The selective activation of STAT3 and STAT5 in T(h)1 cells was associated with differential induction of SOCS molecules. After restimulation, SOCS1 expression was significantly increased in T(h)2 cells, but not in T(h)1 and nonpolarized 'T-h' cells. Additionally, the level of CIS was higher in T(h)2 cells compared with T(h)1 and T-h cells. In contrast, the expression of SOCS3 was higher in T(h)1 cells. The differential induction of SOCS proteins was paralleled by the differential expression of cytokines in re-stimulated T(h)1 and T(h)2 cells (IFN-gamma and IL-4/IL-13 respectively). Our results suggests that STAT3 and STAT5, possibly regulated by the SOCS proteins, may play a role in the differentiation of T-h cells, and in the maintenance of the T(h)1 and T(h)2 phenotype.},
  author       = {Anderson, Per and Sundstedt, A and Li, Li and O'Neill, EJ and Li, Su-Ling and Wraith, DC and Wang, P},
  issn         = {1460-2377},
  keyword      = {cytokine signalling,signal transducer and activator of transcription,suppressor of,T-h},
  language     = {eng},
  number       = {11},
  pages        = {1309--1317},
  publisher    = {Oxford University Press},
  series       = {International Immunology},
  title        = {Differential activation of signal transducer and activator of transcription (STAT)3 and STAT5 and induction of suppressors of cytokine signalling in T(h)1 and T(h)2 cells},
  url          = {http://dx.doi.org/10.1093/intimm/dxg130},
  volume       = {15},
  year         = {2003},
}