Xcl2

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known. A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly (see figure), in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a variety of immune cells, but also by parenchymatous cells. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the formation, homeostasis or proliferation of tissues.

Human XCL2, also known as lymphotactin2, SCYC2 or SCM1beta is a small, 10 kDa glycoprotein of the C chemokine family. XCL1/lymphotactin-1 is a closely related chemokine of the same family that differs from XCL2 only in 2 amino acids, but appears to be subject to separate regulation.

XCL2 and XCL1/lymphotactin-1 bind and activate the G protein-coupled chemokine receptor XCR1 (the coding gene is located on chromosome 1 in humans). This receptor is expressed on dendritic cells and on T and B lymphocytes. Binding of XCL2 to the receptor XCR1 leads to chemotactic migration of these cells.

Also detected is the XCR1 receptor on ovarian cancer (EOC) cells, hepatocellular carcinoma cells, and bronchial carcinoma cells. Thus, XCL1 and XCL2 (among other cytokines) may play a role in the expansion of these tumor cells. In lung carcinoma, the expressivity of XCL2 is correlated with malignancy progression.

XCL2, but not XCL1, is increased in expression by macrophages after activation by an antigen of Mycobacterium tuberculosis (Wag31). Activation of T cells results in a marked increase in chemokines XCL1 and XCL2 in CD8+ T cells. Activated CD4+ T cells express increased levels of XCL2 but not XCL1. These results indicate that both chemokines are regulated independently.

1. Cao W et al (2008) Mycobacterium tuberculosis antigen Wag31 induces expression of C-chemokines XCL2 in macrophages. Curr microbiol 57:189-194.
2. Fox JC et al (2015) Structural and agonist properties of XCL2, the other member of the C-chemokine subfamily. Cytokines 71:302-311.
3. Kim M et al (2012) The lymphotactin receptor is expressed in epithelial ovarian carcinoma and contributes to cell migration and proliferation. Mol Cancer Res 10:1419-1429.
4. Xuan W et al (2015) The chemotaxis of M1 and M2 macrophages is regulated by different chemokines. J Leukoc Biol 97:61-69.
5. Zhou B et al (2016) Expression of chemokines XCL2 and CX3CL1 in lung cancer. Med Sci Monit 22:1560-1565.