Kinetics and STAT4- or STAT6-mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells.
Many genes implicated in Th1 and Th2 differentiation have been identified in both human and mouse. However, the functional roles and hierarchy of these factors in the signaling pathways leading to either Th1 or Th2 responses are less clear. To explore at which stage of polarization the differences between Th1 and Th2 cells occur, we have studied the expression of 23 key genes implicated in the process during the first week of polarization from human precursor T helper cells using quantitative real-time reverse transcription-PCR. According to our results, 14 of the genes were clearly regulated differentially in Th1 and Th2 conditions in distinct time-dependent patterns, either during the first 2 days or after 1 week of polarization. Furthermore, 6 of these genes were identified to be targets of STAT4/6 regulation. Thus, for the first time we demonstrate expression kinetics of a number of key genes involved in Th1 and Th2 differentiation during the first week of polarization in both human and mouse. In addition, our study shows for the first time that the genes BCL-6 and TRADD are differentially regulated during the polarization of human Th1 and Th2 cells.
Lund
Riikka J
RJ
Turku Center for Biotechnology, University of Turku and Abo Akademi, Turku, Finland. riikka.lund@btk.utu.fi
Ylikoski
Emmi K
EK
Aittokallio
Tero
T
Nevalainen
Olli
O
Lahesmaa
Riitta
R
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494091:Stat4 protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4