Chemokines and Chemokine Receptors

Chemokines are a class of cytokines that induce chemotaxis (migration) of target cells. Chemokines work through concentration gradients. Attracted cells move toward areas of higher concentrations of the chemokine. While some chemotaxis is induced by inflammation or damaged cells, other chemokines function in homeostasis.

Chemokines receptors are seven transmembrane spanning G protein-coupled receptors that allow cells to migrate towards increasing chemokine gradients. The receptor N-terminus is external and contributes to ligand binding while the carboxy terminus (COOH) allows for interaction with signaling molecules and downstream signaling.

Homeostasis:

Homeostatic chemokines are constitutively expressed in particular organs or tissues. Specific chemokine receptors are often required to gain entry (or exit) from certain organs and tissues like the thymus and bone marrow. These chemokines also have a more diverse range of functions compared to inflammatory chemokines. These functions include organogenesis, stem cell migration, and cell development. Due to their function of targeting cells to specific organs, homeostatic chemokines can also be involved in cancer and metastasis.

For more information on homeostatic chemokines, see the review below:
Zlotnik, A. et al. 2011. Nat. Rev. Immunol. 11:597. Pubmed

Inflammation:

In the event of infection, injury, or tissue damage, inflammatory chemokines are often released to address the problem. Many inflammatory chemokines attract a wide variety of cells in both the innate and adaptive arms of immunity. Upon sensing the inflammatory chemokine, cells will extravasate from the blood vessel and follow the gradient to its source. Once at the site of injury, immune cells can react by releasing additional cytokines and chemokines, bringing more cells into the fold. Chemokines are also involved in the orchestration of wound healing.

For more information on inflammatory chemokines, see the review below:
Moser, B. and Willimann, K. 2004. Ann. Rheum. Dis. 63:84. Pubmed

Chemokine Structure and Classification
	Relatively small size (8-14 kDa) Produced in very large amounts to establish concentration gradients for responding cells to migrate. Chemokines contain several (usually four) cysteines in conserved positions. These cysteines provide tertiary structure for the chemokine through disulfide bonds. The spacing between the first two cysteines determines the type of chemokine.

Chemokine Receptor Structure

Seven transmembrane regions
Amino terminus (NH2) and extracellular loops contribute to the ligand specificity.
G-coupled proteins at the carboxy terminus (COOH) allow for downstream signaling.

SH Park et al. Nature 491, 779 (2012) doi:10.1038/nature11580

Three-dimensional structure of CXCR1.

Chemokine Receptor Biology poster

Order your copy of our poster here. Click on the image below to view the interactive pathway.

Receptor-Ligand Table

Use this table to quickly identify the chemokines that bind to each receptor. Click on the receptor to sort the ligands to the top.

Ligand	CXCR1	CXCR2	CXCR3	CXCR4	CXCR5	CXCR6	CXCR7	CX3CR1	XCR1	CCR1	CCR2	CCR3	CCR4	CCR5	CCR6	CCR7	CCR8	CCR9	CCR10
CXCL1	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL2	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL3	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL5	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL6	a	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL7	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL8	a	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL9	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL10	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL11	b	b	a	b	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b
CXCL12	b	b	b	a	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b
CXCL13	b	b	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b	b
CXCL16	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b	b	b	b	b
CX3CL1	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b	b	b
XCL1	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b	b
XCL2	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b	b
CCL1	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b
CCL2	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b
CCL3	b	b	b	b	b	b	b	b	b	a	b	b	b	a	b	b	b	b	b
CCL3L1	b	b	b	b	b	b	b	b	b	a	b	b	b	a	b	b	b	b	b
CCL4	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b
CCL5	b	b	b	b	b	b	b	b	b	a	b	a	b	a	b	b	b	b	b
CCL7	b	b	b	b	b	b	b	b	b	a	a	a	b	b	b	b	b	b	b
CCL8	b	b	b	b	b	b	b	b	b	a	a	a	b	a	b	b	b	b	b
CCL11	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b
CCL13	b	b	b	b	b	b	b	b	b	a	a	a	b	b	b	b	b	b	b
CCL14	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b
CCL15	b	b	b	b	b	b	b	b	b	a	b	a	b	b	b	b	b	b	b
CCL16	b	b	b	b	b	b	b	b	b	a	a	b	b	b	b	b	b	b	b
CCL17	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b
CCL19	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b
CCL20	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b
CCL21	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b
CCL22	b	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b
CCL23	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b	b	b
CCL24	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b
CCL25	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a	b
CCL26	b	b	b	b	b	b	b	b	b	b	b	a	b	b	b	b	b	b	b
CCL27	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a
CCL28	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	b	a

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