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 fu nction is intimately connected with the acquisition of new migratory capaci ties, as exemplified by differential expression of chemokine receptors. Thi s study investigates the molecular mechanisms responsible for Th2-restricte d 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 c ontains a positive regulatory element. A strong negative element was also l ocalized in the flanking intronic sequence. The study further investigates the role of chromatin remodeling in the regulation of this Th2-specific gen e. Drugs that affect the chromatin structure facilitate CCR3 expression in T cells. Furthermore, in differentiating Th2 cells, selected regions are as sociated with acetylated-H3 histones and become more accessible to DNase I. These results suggest that in Th2 cells both cytokine production and migra tory capacity are regulated through a similar mechanism involving chromatin remodeling. (Blood. 2001;98:2568-2570) (C) 2001 by The American Society of Hematology.