Identification of genes involved in the initiation of human Th1 or Th2 cell commitment.
The differentiation of naïve T helper (Th) cells is induced by TCR activation and IL-12/STAT4 or IL-4/STAT6 signaling pathways, forming Th1 and Th2 cells, respectively. In this study, oligonucleotide arrays were used to identify genes regulated during the initiation of human Th1 and Th2 cell differentiation at 2 and 6 h in presence or absence of immunosuppressive TGF-beta. As a result the immediate targets of IL-12, IL-4 and TGF-beta were identified. The effects of IL-12 at this early stage were minimal and consistent with the known kinetics of IL-12Rbeta2 expression. IL-4, however, was observed to rapidly regulate 63 genes, 26 of which were differentially expressed at both the 2- and 6-h time points. Of these IL-4 regulated genes, one-third have previously been observed to display expression changes in the later phases of the polarization process. Similarly to the key regulators, TBX21 and GATA3, the transcription factors SATB1, TCF7 and BCL6 were differentially regulated at the protein level during early Th1 and Th2 cell polarization. Moreover, the developing Th1 and Th2 cells were demonstrated to be responsive to the immunosuppressive TGF-beta and IL-10. In this study, a panel of novel factors that may be important regulators of the differentiation process was identified.
Lund
Riikka
R
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Turku, Finland.
Ahlfors
Helena
H
Kainonen
Essi
E
Lahesmaa
Anna-Maria
AM
Dixon
Craig
C
Lahesmaa
Riitta
R
D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D036961:Matrix Attachment Region Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015238:Sulfotransferases / Q000096:biosynthesis / Q000235:genetics; D051822:T Cell Transcription Factor 1 / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000502:physiology*; D018418:Th2 Cells / Q000166:cytology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D000097811:Carbohydrate Sulfotransferases
D004268:DNA-Binding Proteins; D051796:Inhibitor of Differentiation Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D036961:Matrix Attachment Region Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015238:Sulfotransferases; D051822:T Cell Transcription Factor 1; D016212:Transforming Growth Factor beta; C084103:BCL6 protein, human; C499363:NKG7 protein, human; C076189:SATB1 protein, human; C497576:TCF7 protein, human; C075640:ID3 protein, human; C499549:CHST10 protein, human; D000097811:Carbohydrate Sulfotransferases