Signaling pathways that lead to the silencing of the interleukin-4-producing potential in Th1 cells.
In order to develop the most effective Th1 immunity, naïve CD4(+) T cells must acquire the capacity to induce the expression of IFN-gamma and to silence Th2 cytokine-producing potential. Although the IFN-gamma-STAT1 and the IL-12-STAT4 pathways have been demonstrated to be important in inducing the IFN-gamma-producing capacity in Th1 cells, their respective roles in silencing the IL-4-producing potential in Th1 cells remain unclear. In this study, we investigated the role of the IFN-gamma and the IL-12 pathways in silencing the IL-4-producing potential in Th1 cells. We found that IFN-gamma was essential to silence the IL-4-producing potential in Th1 cells, while IL-12 only partially suppressed the IL-4-producing potential. IFN-gamma depended on STAT1 and IL-12 depended on STAT4 to suppress the IL-4-producing potential. We showed that the IL-12-STAT4 pathway and the IFN-gamma-STAT1 pathway converge at the point of T-bet. Our study demonstrates that the IFN-gamma-STAT1-T-bet signaling pathway is the major pathway that leads to silencing the IL-4-producing potential of Th1 cells.
Zhuang
Yonghua
Y
Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Huang
Zan
Z
Nishida
Jun
J
Zhang
Lin
L
Huang
Hua
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D020868:Gene Silencing; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma