CCL21

CCL21, or C-C motif chemokine ligand 21, is a chemokine of the C-C family that plays a key role in the organization and function of secondary lymphoid tissues. It is also known as secondary lymphoid-tissue chemokine (SLC). The human CCL21 gene encodes a protein produced mainly by lymphatic endothelial cells and fibroblastic reticular cells within lymphoid tissues. CCL21 is closely related to CCL19, and together they signal through the CCR7 receptor.

Function and mechanism

CCL21 guides the migration of CCR7-expressing cells, including naive T cells and mature dendritic cells, to lymph nodes and other secondary lymphoid organs. It contributes to the formation of chemokine gradients along lymphatic vessels and within lymphoid tissue that direct cells to appropriate zones, promoting efficient immune surveillance and initiation of adaptive immune responses. A distinctive feature of CCL21 is its basic, glycosaminoglycan-binding C-terminus, which facilitates immobilization on extracellular matrices and endothelial surfaces, creating a largely immobilized gradient that complements soluble chemotaxis.

Clinical and research relevance

Altered CCL21 expression or CCR7 signaling can affect immune cell trafficking and has been studied in the contexts of infection, cancer metastasis to lymph nodes, and autoimmunity. In tumors, CCL21 expression by stromal or endothelial cells may influence lymphocyte infiltration and anti-tumor immunity, making the axis a potential consideration in immunotherapeutic strategies. Owing to its central role in lymphoid tissue homing, CCL21 remains a focus of research on lymphocyte trafficking and immune system organization.