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.
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 re-stimulation, SOCS1 expression was significantly increased in T(h)2 cells, but not in T(h)1 and non-polarized '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.
Anderson
Per
P
Institute of Cell and Molecular Sciences, Barts and The London School of Medicine and Dentistry, London EC1A 7ED, UK. Per.Anderson@wblab.lu.se
Sundstedt
Anette
A
Li
Li
L
O'Neill
Emma J
EJ
Li
Suling
S
Wraith
David C
DC
Wang
Ping
P
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053613:Janus Kinase 1; D051379:Mice; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis
D015704:CD4 Antigens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1