![]() Gene knockout mice lacking CCR7 or CCR7 ligands show marked impairment of T cell migration into lymphoid organs, indicating that CCR7 signaling is indispensable for T cell recruitment in vivo 3. CCR7 interacts with CCR7 ligands (CCL19 and CCL21) expressed mainly in the high endothelial venules (HEVs) and lymph node parenchyma 3. CCR7 is one of the major chemokine receptors preferentially expressed in a wide range of immune cells, including naïve T and B cells, central memory T cells, mature dendritic cells 3, and plasmacytoid dendritic cells 4, 5. This process is tightly regulated by the interaction between lymphoid chemokines expressed in lymphoid tissues and their specific G-protein-coupled receptors in migrating cells 1, 2. Recruitment of lymphocytes from the blood into secondary lymphoid tissues is a process contributing to continuous immune surveillance. Our study indicates that CCR7 homodimerization critically regulates CCR7 ligand-dependent cell migration and intracellular signaling in multiple cell types. In contrast, dissociation of CCR7 homodimerization by a novel CCR7-derived synthetic peptide attenuated CCR7-dependent cell migration, ligand-dependent CCR7 internalization, ligand-induced actin rearrangement, and Akt and Erk signaling in CCR7-expressing cells. Induction of stable CCR7 homodimerization resulted in enhanced CCR7-dependent cell migration and CCL19 binding, whereas induction of CXCR4/CCR7 heterodimerization did not. Here, by inducing or disrupting CCR7 dimers, we demonstrated a direct contribution of CCR7 homodimerization to CCR7-dependent cell migration and signaling. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. ![]()
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