CCR7

CCR7, or C-C chemokine receptor type 7, is a chemokine receptor that belongs to the family of G protein-coupled receptors. It is activated by the chemokines CCL19 (MIP-3β) and CCL21 (6Ckine). In humans, the receptor is encoded by the CCR7 gene. The receptor is expressed on a range of immune cells, including naive and central memory T cells, regulatory T cells, B cells, and mature dendritic cells, with thymocytes and some NK cells also showing expression. This expression pattern supports a primary role in lymphoid tissue trafficking rather than overt inflammation at peripheral sites.

Functionally, CCR7 directs the migration of immune cells to secondary lymphoid organs, especially lymph nodes, by guiding them along gradients of CCL19 and CCL21 produced by stromal cells and high endothelial venules. This trafficking is essential for antigen presentation, T cell activation, and the initiation of adaptive immune responses. CCR7 signaling fosters dendritic cell migration to lymph nodes and helps retain T cells in T cell–rich zones; deficiency of CCR7 impairs dendritic cell migration and T cell priming. The receptor also contributes to thymic T cell development and central tolerance.

Signaling and regulation: CCR7 is a G protein-coupled receptor that signals primarily through Gαi proteins, triggering calcium mobilization and activation of downstream pathways such as MAPK, leading to cytoskeletal changes that drive chemotaxis. Receptor activity is modulated by desensitization and internalization mediated by β-arrestins.

Clinical and research relevance: Elevated CCR7 expression on some tumor cells has been associated with lymph node metastasis, making the axis a potential therapeutic target in cancer. In immunotherapy and vaccine development, manipulating CCR7 function aims to optimize dendritic cell and T cell trafficking to lymph nodes. Mouse and human studies show that CCR7 deficiency disrupts lymph node homing and dampens immune responses.