Biochemical and Biophysical Research Communications, Vol.288, No.5, 1188-1193, 2001
Induction of CCR7 expression in thymocytes requires both ERK signal and Ca2+ signal
CC chemokine receptor 7 (CCR7) expression is crucial for thymocyte trafficking across the corticomedullary junction in the thymus and for lymph node homing of naive T cells. However, the induction mechanism of CCR7 expression is vastly unknown. In isolated CD4(+)CD8(+)CCR7(-) thymocytes, a moderate 20-h pulse stimulation with a combination of the calcium ionophore ionomycin and the protein kinase C activator phorbol myristate acetate induced CCR7 expression and CD8 downregulation. Similar changes were induced in a CD4(+)CD8(+)CCR7(-) T cell line upon stimulation with the same combination of reagents, but not with either one alone. These changes were inhibited by U0126, an inhibitor of the extracellular signal-regulated kinase kinase (ERKK/MEK). The transfectants expressing a constitutively active form of the MEK kinase Raf-1 became CD4(+)CD8(+)CCR7(+) upon stimulation with ionomycin alone. Thus, Raf-1-mediated signals and Ca2+-dependent signals are essential to induce CCR7 expression in CD4(+)CD8(+) T cells and thymocytes as well as their differentiation.