chemokine

Chemokines are a family of small secreted cytokines that regulate leukocyte migration. They are usually 8–12 kilodaltons in size and are characterized by conserved cysteine residues that form one of several motifs (CC, CXC, CX3C, or XC). Binding to chemokine receptors, a subset of G protein-coupled receptors, they create chemotactic gradients that direct the movement of immune cells toward sites of infection or injury.

Based on the arrangement of their first two cysteine residues, chemokines are grouped into CC, CXC, CX3C, and XC subfamilies. Corresponding receptors are named CCR, CXCR, CX3CR1, and XCR1. Examples include CCL2 (MCP-1), CCL5 (RANTES), CXCL8 (IL-8), and CXCL12 (SDF-1).

Chemokines function in guiding leukocytes to sites of inflammation, during development of lymphoid organs, wound healing, and tumor biology; they influence leukocyte trafficking including neutrophils, monocytes, T cells, NK cells, and dendritic cells; signaling via GPCR triggers intracellular cascades (Ca2+, PI3K, MAPK).

Produced by a wide range of cells including macrophages, dendritic cells, T cells, endothelial cells, fibroblasts, and epithelial cells in response to pathogens and cytokines (IL-1, TNF, microbial products). Dysregulated chemokine signaling is implicated in autoimmune diseases, chronic inflammation, and cancer metastasis.

Chemokine receptors are therapeutic targets; CCR5 antagonists are used in HIV treatment; modulators of CXCR4 (plerixafor) are used to mobilize hematopoietic stem cells; research continues on their potential for treating inflammatory diseases and cancer.