CXCL10 gene

The CXCL10 gene (CXCL10 stands for: C-X-C Motif Chemokine Ligand 10) is a protein-coding gene located on chromosome 4q21.1. An important paralog of this gene is CXCL9.

The CXCL10 gene is an antimicrobial gene that encodes a chemokine of the CXC subfamily. This chemokine is a ligand for the receptor CXCR3. Binding of the CXCL10 protein to CXCR3 leads to pleiotropic effects, including stimulation of monocytes, migration of natural killer and T cells, and modulation of adhesion molecule expression.

The CXCL10 chemokine is a pro-inflammatory cytokine involved in a variety of processes such as chemotaxis, differentiation and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects (Angiolillo AL et al. 1995; Sidahmed AM et al. 2012). The cytokine thus plays an important role in viral infections by stimulating the activation and migration of immune cells to the infected sites.

Mechanistically, binding of CXCL10 to the CXCR3 receptor activates G protein-mediated signaling and leads to downstream activation of the phospholipase C-dependent pathway, an increase in intracellular calcium production and actin reorganization (Smit MJ et al. 2003). In turn, activated Th1 lymphocytes are recruited to the sites of inflammation (Cheeran MC et al. 2003).

Activation of the CXCL10/CXCR3 axis also plays an important role in neurons in response to brain injury by activating and directing microglia, the resident macrophage population of the central nervous system, to the site of the lesion. This recruitment is an essential element for neuronal reorganization.

Torok et al. reported an upregulation of the CXCL10 gene in pediatric patients with circumscribed scleroderma.

1. Angiolillo AL et al. (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182:155-162.
2. Cheeran MC et al. (2003) CXCL10 production from cytomegalovirus-stimulated microglia is regulated by both human and viral interleukin-10. J Virol 77:4502-4515.
3. Sidahmed AM et al. (2012) CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro. Cytokine 59:433-41.
4. Smit MJ et al. (2003) CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood 102:1959-1965.
5. Torok KS et al. (2015) Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles. Semin Arthritis Rheum 45:284-293.