Regulation of ST2L expression on T helper (Th) type 2 cells.
T1/ST2L, an IL-1 receptor homologue, is selectively expressed on murine Th2 cells and specific anti-ST2L antibodies can profoundly modulate the Th1/Th2 balance in vivo. Naive CD4+ T cells do not express ST2L but do so on activation with specific antigen in the presence of IL-4 or when stimulated with low doses of antigen in the absence of exogenously added IL-4. Similarly enhanced ST2L expression occurred after stimulation of Th2 cells with antigen or the mitogen ConA in the presence of APC. Restimulation of Th2 cells in the presence of IFN-gamma led to a decreased expression of ST2L to below basal levels. Conversely, Th2 cells cultured with IL-4 led to increased ST2L expression. The reduced expression of ST2L in response to high doses of antigen is also reversed by the neutralization of IFN-gamma. Using an ST2L promoter/luciferase reporter gene construct, we show that the distal but not proximal ST2L promoter is responsible for specific gene expression in Th2 cells. IL-4 enhances, whereas IFN-gamma suppresses ST2L expression via direct modulation of the distal promoter of the ST2L gene. These data provide a mechanistic explanation for the selective expression of ST2L on Th2 cells.
Carter
R W
RW
Department of Virology, St Bartholomew's and Royal London School of Medicine and Dentistry, QMW College, University of London, London, GB.
Sweet
M J
MJ
Xu
D
D
Klemenz
R
R
Liew
F Y
FY
Chan
W L
WL
D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015847:Interleukin-4 / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D018123:Receptors, Interleukin; D018418:Th2 Cells / Q000378:metabolism*
C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin