Cytokines and chemokines are used in research and development to activate, modulate, and differentiate cells in their efforts to better understand immune cell function and/or create cell-based therapeutics. Learn about the properties and functions of these important cell signaling proteins.
What are cytokines?
Cytokines are small proteins secreted by cells that enable cell-cell communication through pathway signaling. Different classes of cytokines have functions such as modulating inflammation, initiating cell proliferation or cellular differentiation. Most cytokines and chemokines are produced by T cells and other white blood cells and thus are important for immune system function, but they also influence processes throughout the body. In addition to immune response, cytokines can modulate bone formation, angiogenesis, cell cycle, apoptosis, and more.
Learn about pro-inflammatory cytokines
Explore cytokine signaling pathways
What are chemokines?
Chemokines (chemotactic cytokines) are a specific family of cytokines that cause immune cells to be attracted and migrate to one another. Chemokine ligands and receptors are important in immune system function, especially for T cells, as well as for cells like macrophages and dendritic cells that must migrate to perform their functions. Chemokines influence other cellular processes such as angiogenesis, embryonic development, and cell-cell adhesion, and exert their effects through G-protein coupled receptors.
Cytokine vs chemokine—what’s the difference?
Chemokines are a structurally defined subset of cytokines. Whereas both cytokines and chemokines are small, soluble proteins excreted by cells, chemokines are distinguished by the presence of a conserved motif of cysteine residues that form disulfide bonds in the functional protein.
Chemokine subfamilies and nomenclature
Chemokines exhibit one of four related structural motifs as shown and described below.
Figure 1. The four types or motifs of chemokines are defined by their structures.
C Chemokines: Contain two conserved cysteine residues linked by a single disulfide bond.
CC Chemokines: Members of this largest group of chemokines contain four conserved cysteine residues of which the two closest to the N-terminus are adjacent to one another (so the sequence contains CC).
CXC Chemokines: The second largest group comprises sequences with four conserved cysteine residues of which the two closest to the N-terminus are separated by a single amino acid.
CX3C Chemokines: Contains four conserved cysteine residues, of which the two closest to the N-terminus are separated by three amino acids.
Examples of chemokines
CXCL6, also known as GCP-2 in humans or LIX in mice, is a connective tissue-derived CXCL chemokine that signals through the CXCR1 and CXCR2 receptors. Expressed in monocytes, platelets, endothelial cells, and mast cells, CXCL6 is a highly selective chemoattractant of neutrophils and exhibits anti-angiogenic activity that suggests cancer-fighting potential.
Eotaxin (CCL11) is a CCL chemokine produced by IFN-γ-stimulated endothelial cells and TNF-activated monocytes that signals through the CCR3 receptor. Eotaxin selectively chemoattracts eosinophils and, along with eotaxin-2 and eotaxin-3, plays a key role in the regulation of eosinophil recruitment in asthmatic lung and allergic reactions.
CXCL1, also known as GRO-α/MGSA in humans, KC in mice and CINC-1 in rats, is a CXCL chemokine secreted predominately by splenic cells that contributes to neutrophil activation during inflammation. CXCL1 also contributes to melanoma-related pathogenesis through stimulation of mitogenesis.
RANTES (CCL5) is a CCL chemokine that can signal through the CCR1, CCR3, CCR5, and US28 (cytomegalovirus) receptors. A chemoattractant of monocytes, memory T cells (CD4+/CD45RO), basophils, and eosinophils, RANTES also has the capability to inhibit certain strains of HIV-1, HIV-2, and SIV.
Chemokines with alternate names, receptors, and responding cell type(s)
Systematic name | Functional name(s) (mouse protein) | Responding cell type(s) (mouse protein) | Known receptor(s) |
---|
CCL1 | I-309 (TCA-3) | iDC, actT [Th2], Mo (PMN) | CCR8 |
CCL2 | MCP-1, MCAF, JE | Bs, Mo, actT, NK, iDC | CCR2, CCR4 |
CCL3 | MIP-1α, LD78α | Eo, Mo, actT, NK, iDC (PMN) | CCR1, CCR4, CCR5 |
CCL3L1 | LD78β | Mo, actT, B | CCR1, CCR3, CCR5 |
CCL4 | MIP-1β, LAG-1 | Mo, actT [Th1], NK, iDC | CCR5 |
CCL4L1 | LAG-1 gene duplication | Mo | CCR1, CCR5 |
CCL5 | RANTES | Eo, Bs, Mo, actT, NK, iDC, Tm | CCR1, CCR3, CCR4, CCR5 |
CCL6 | C10 | Mo | CCR1 |
CCL7 | MCP-3 (FIC) | Eo, Bs, Mo, actT, NK, iDC | CCR1, CCR2, CCR3 |
CCL8 | MCP-2 | Eo, Bs, Mo, actT, NK, iDC | CCR1, CCR2B, CCR3, CCR5 |
CCL9/10 | MIP-1γ, MRP-2 | (PMN, actT) | CCR1 |
CCL11 | Eotaxin | Eo, Bs, actT [Th2], iDC | CCR3 |
CCL12 | MCP-5 | Eo, Bs, Mo, actT, NK, iDC | CCR2 |
CCL13 | MCP-4, CKβ-10 | Eo, Bs, Mo, actT, NK, iDC | CCR1, CCR2, CCR3 |
CCL14 | HCC-1 | Eo, Mo, T | CCR1, CCR3, CCR5 |
CCL15 | MIP-5, MIP-1d, HCC-2, LKN-1 | Mo, T | CCR1, CCR3 |
CCL16 | LEC, HCC-4 | Mo, actT [Th1] | CCR1 |
CCL17 | TARC (ABCD-2) | actT [Th2] | CCR4 |
CCL18 | MIP-4, DC-CK1, PARC, AMAC-1 | Tr, iDC | unknown |
CCL19 | MIP-3β, ELC, Exodus-3, CKβ-11 | Tr, actT, mDC | CCR7 |
CCL20 | MIP-3α, LARC, Exodus-1 | Tm, B, iDC, PMN | CCR6 |
CCL21 | Exodus-2, 6Ckine, SLC | Tr, actT, mDC | CCR7 |
CCL22 | MDC, STCP-1 (ABCD-1) | Mo, actT [Th2], NK, iDC | CCR4 |
CCL23 | MIP-3, MPIF-1, CKβ-8 | PMN, Mo, Tr | CCR1 |
CCL24 | Eotaxin-2, MPIF-2, CKβ-6 | Eo, Bs, actT [Th2], iDc, PMN, Tr | CCR3 |
CCL25 | TECK | Thymocytes, Tr, iDC | CCR9 |
CCL26 | MIP-4α, Eotaxin-3 | Eo, Bs, actT [Th2], iDC | CCR3 |
CCL27 | CTACK, ILC, Eskine | actT | CCR10 |
CCL28 | MEC | actT, Tr, Eo | CCR3, CCR10 |
Systematic name | Functional name(s) (mouse protein) | Responding cell type(s) (mouse protein) | Known receptor(s) |
---|
CXCL1 | GRO1, GRO-α, MGSA, NAP-3 (KC) | PMN | CXCR1, CXCR2 |
CXCL2 | GRO2, GRO-β, MIP2-α (MIP-2) | PMN | CXCR1, CXCR2 |
CXCL3 | GRO3, GRO-γ, MIP2-β (DCIP-1) | PMN | CXCR2 |
CXCL4 | PF-4, Oncostatin-A | PMN, Mo | CXCR3B |
CXCL5 | ENA-78 | PMN | CXCR2 |
CXCL6 | GCP-2, LIX, CKA-3 | PMN | CXCR1, CXCR2 |
CXCL7 | NAP-2, PBP, LDGF, MDGF | PMN | CXCR1, CXCR2 |
CXCL8 | IL-8, GCP-1, NAP-1 | PMN, Bs | CXCR1, CXCR2 |
CXCL9 | MIG | actT [Th1], NK | CXCR3 |
CXCL10 | IP-10 (CRG-2) | Mo, actT [Th1], NK | CXCR3 |
CXCL11 | I-TAC, IP-9 | actT [Th1], NK | CXCR3, CXCR7 |
CXCL12 | SDF-1, SDF-1α/β, PBSF | All cell types | CXCR4, CXCR7 |
CXCL13 | BCA-1, BLC | B, (Mo) | CXCR5 |
CXCL14 | BRAK, MIP-2G | PMN, mDC (B, Mo) | unknown |
CXCL15 | (Lungkine) | PMN | unknown |
CXCL16 | SR-PSOX | actT | CXCR6 |
CXCL17 | VEGF co-regulated chemokine 1, DMC | Mo, iDC | unknown |
Systematic name | Functional name(s) (mouse protein) | Responding cell type(s) (mouse protein) | Known receptor(s) |
---|
XCL1 | Lymphotactin, ATAC, SCM-1 | Tr | XCR1 |
XCL2 | SCM-1β | Tr | XCR1 |
CX3CL1 | Fractalkine, Neurotactin, CX3C | Mo, actT, NK | CX3CR1 |
Key to cell types:
Tm = Memory T cells Bs = Basophils Eo = Eosinophils PMN = Neutrophils | B = B cells Tr = Resting T cells NK = Natural killer cells mDC = Mature dendritic cells | actT = Activated T cells T = T cells Mo = Monocytes iDC = Immature dendritic cells |
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