Molecular regulation of CC-chemokine receptor 3 expression in human T helper 2 cells.
In developing T helper 1 (Th1) and Th2 cells the acquisition of effector function is intimately connected with the acquisition of new migratory capacities, as exemplified by differential expression of chemokine receptors. This study investigates the molecular mechanisms responsible for Th2-restricted expression of the CC-chemokine receptor 3 (CCR3). The minimal promoter in T cells was identified in the -149 base pair (bp) upstream sequence that contains a positive regulatory element. A strong negative element was also localized in the flanking intronic sequence. The study further investigates the role of chromatin remodeling in the regulation of this Th2-specific gene. Drugs that affect the chromatin structure facilitate CCR3 expression in T cells. Furthermore, in differentiating Th2 cells, selected regions are associated with acetylated-H3 histones and become more accessible to DNase I. These results suggest that in Th2 cells both cytokine production and migratory capacity are regulated through a similar mechanism involving chromatin remodeling.
Scotet
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E
Basel Institute for Immunology, Basel, Switzerland. emmanuel.scotet@nantes.inserm.fr
Schroeder
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S
Lanzavecchia
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A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002843:Chromatin / Q000502:physiology; D017931:DNA Primers; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000235:genetics*; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
C515350:CCR3 protein, human; D002843:Chromatin; D017931:DNA Primers; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D003850:Deoxyribonuclease I