What are Chemokines?
Chemokines are a family of chemoattractant cytokines with essential roles in inflammation and homeostasis. To date, almost 50 different chemokines have been discovered, and are grouped into four main sub-families (CC, CXC, CX3C, and XC) based on the number and arrangement of conserved cysteine residues. Chemokines exert their biological effects by binding to complementary chemokine receptors within the G protein coupled receptor (GPCR) family. While some chemokines are proinflammatory, serving to recruit immune cells to the site of tissue damage or an infection, others are homeostatic and involved in controlling cell migration during normal tissue development or maintenance.
Chemotactic Cytokines
Chemokines, also known as chemotactic cytokines, are a diverse family of small signaling proteins critical for immune system function. They play a central role in directing the migration of cells, particularly white blood cells (leukocytes), to sites of inflammation, infection, or injury. This resource page provides an overview of chemokines, their classification, functions, and implications in health and disease.
Chemokines are secreted proteins that signal through G protein-coupled receptors (GPCRs) on the surface of target cells. Their primary function is to regulate cell movement (chemotaxis), guiding immune cells to specific locations in the body. Beyond chemotaxis, chemokines also influence processes such as cell adhesion, immune surveillance, and tissue repair [1,2].
Chemokines are secreted proteins that signal through G protein-coupled receptors (GPCRs) on the surface of target cells. Their primary function is to regulate cell movement (chemotaxis), guiding immune cells to specific locations in the body. Beyond chemotaxis, chemokines also influence processes such as cell adhesion, immune surveillance, and tissue repair [1,2].
Functions of Chemokines
Immune Cell Migration
The most recognized function of chemokines is directing immune cells to areas where they are needed:
Cellular Adhesion and Arrest
Chemokines facilitate leukocyte adhesion to endothelial cells during extravasation—the process by which immune cells exit blood vessels to reach tissues [1].
Tissue Development and Repair
Some chemokines play roles in organ development, angiogenesis (formation of blood vessels), and wound healing.
Chemokine Receptors
Chemokine receptors are GPCRs that mediate the effects of chemokines. They are divided into two main categories:
Regulation of Chemokine Activity
Chemokine activity is tightly regulated by:
The most recognized function of chemokines is directing immune cells to areas where they are needed:
- Inflammation: Chemokines recruit leukocytes to sites of infection or tissue damage.
- Immune Surveillance: They help maintain immune homeostasis by guiding lymphocytes through lymphoid tissues.
Cellular Adhesion and Arrest
Chemokines facilitate leukocyte adhesion to endothelial cells during extravasation—the process by which immune cells exit blood vessels to reach tissues [1].
Tissue Development and Repair
Some chemokines play roles in organ development, angiogenesis (formation of blood vessels), and wound healing.
Chemokine Receptors
Chemokine receptors are GPCRs that mediate the effects of chemokines. They are divided into two main categories:
- Conventional Chemokine Receptors (cCKRs): These receptors transduce signals that lead to cell migration and other biological responses.
- Atypical Chemokine Receptors (ACKRs): These regulate chemokine availability and gradients without inducing cell migration directly [1,2].
Regulation of Chemokine Activity
Chemokine activity is tightly regulated by:
- Post-Translational Modifications: Proteolytic cleavage or chemical modifications can alter receptor binding or activity.
- Glycosaminoglycan Binding: Interaction with extracellular matrix components like glycosaminoglycans helps immobilize chemokines and maintain concentration gradients.
- Oligomerization: Chemokines can form dimers or higher-order structures that influence their function [1].
Structure and Classification
Chemokines are classified based on the arrangement of conserved cysteine residues in their protein structure:
- CC Chemokines: Characterized by two adjacent cysteines. These primarily attract monocytes, T cells, and dendritic cells.
- CXC Chemokines: Contain one amino acid between two cysteines. They are often involved in neutrophil recruitment.
- CX3C Chemokines: Feature three amino acids between two cysteines. The only member, CX3CL1 (fractalkine), has both adhesive and chemoattractant properties.
- XC Chemokines: Lack the first and third cysteines found in other subfamilies [1,2].
Clinical Implications
Dysregulated chemokine signaling is implicated in numerous diseases:
- Autoimmune Disorders: Excessive recruitment of immune cells can exacerbate conditions like rheumatoid arthritis or multiple sclerosis.
- Cancer: Tumors exploit chemokine pathways to promote angiogenesis and metastasis.
- Infectious Diseases: Pathogens like HIV use chemokine receptors (e.g., CCR5) for entry into host cells [1,2].
Challenges for chemokine research
A major challenge for chemokine research stems from redundancy in ligand-receptor binding. Just 19 chemokine receptors have so far been identified (less than half the number of known chemokines), many of which can bind multiple ligands. For example, the chemokine receptor CCR1 has been reported to bind up to 12 distinct chemokines, while CXCR1 and CXCR2 share at least three ligands, including CXCL6, CXCL7, and CXCL8, all of which have different functions. Further hurdles are encountered when expressing and purifying chemokines, since it can often be difficult to maintain bioactivity due to the inherent instability of chemokine molecules.
Chemokines are indispensable for immune system function and tissue homeostasis. Understanding their complex signaling networks provides valuable insights into developing therapies for inflammatory diseases, cancer, and beyond. For more information about our protein reagents related to chemokine research, please explore our product catalog tailored for immunology and cell biology applications.
References
[1] https://www.musechem.com/blog/recent-research-on-chemokines-and-chemokine-receptors/
[2] https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d0a47ea4e53c4876098e72/original/membrane-proteins-challenging-biotherapeutic-targets.pdf
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC6120486/
[4] https://pubmed.ncbi.nlm.nih.gov/29637711/
[5] https://www.imrpress.com/journal/FBL/25/7/10.2741/4860/htm
[6] https://www.azolifesciences.com/article/Role-of-Chemokines-and-Cytokines-in-Health-and-Disease.aspx
[7] https://terra-docs.s3.us-east-2.amazonaws.com/IJHSR/Articles/volume6-issue12/IJHSR_2024_612_34.pdf
[8] https://scholarcommons.sc.edu/cgi/viewcontent.cgi?article=1297&context=jscas
[2] https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d0a47ea4e53c4876098e72/original/membrane-proteins-challenging-biotherapeutic-targets.pdf
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC6120486/
[4] https://pubmed.ncbi.nlm.nih.gov/29637711/
[5] https://www.imrpress.com/journal/FBL/25/7/10.2741/4860/htm
[6] https://www.azolifesciences.com/article/Role-of-Chemokines-and-Cytokines-in-Health-and-Disease.aspx
[7] https://terra-docs.s3.us-east-2.amazonaws.com/IJHSR/Articles/volume6-issue12/IJHSR_2024_612_34.pdf
[8] https://scholarcommons.sc.edu/cgi/viewcontent.cgi?article=1297&context=jscas
