Induction of CCR7 expression in thymocytes requires both ERK signal and Ca(2+) 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 Ca(2+)-dependent signals are essential to induce CCR7 expression in CD4+CD8+ T cells and thymocytes as well as their differentiation.
Adachi
S
S
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo 194-8511, Japan.
Kuwata
T
T
Miyaike
M
M
Iwata
M
M
D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D002478:Cells, Cultured; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000145:classification; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D015533:Transcriptional Activation
D016827:CD8 Antigens; C515371:Ccr7 protein, mouse; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases