CXCR6 gene

The CXCR6 gene (CXCR6 stands for: C-X-C Motif Chemokine Receptor 6) is a protein-coding gene located on chromosome 3p21.31. The protein encoded by this gene is a G-protein-coupled receptor with seven transmembrane domains that belongs to the CXC chemokine receptor family. This family also includes the CXC chemokine receptors CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CXCR7.

The CXCR6 gene, which is mapped on the chemokine receptor gene cluster, is expressed in several T lymphocyte subsets and bone marrow stromal cells. The encoded protein and its exclusive ligand, chemokine ligand 16 (CCL16), are part of a signaling pathway that regulates the migration of T lymphocytes to various peripheral tissues (liver, spleen, red pulp, intestine, lung and skin) and promotes cell-cell interaction with dendritic cells and fibroblastic reticulum cells. CXCR6/CCL16 also controls the localization of resident memory T lymphocytes in different compartments of the lung and maintains resident memory T lymphocytes of the airways, which represent an important first line of defense against respiratory pathogens.

The encoded CXCR6 receptor protein serves as an entry coreceptor used by HIV-1 and SIV (SIV stands for "Simian Immunodeficiency Virus," a virus that primarily infects monkeys and other primates. It is a closely related virus to HIV that infects humans. SIV is often used in research to understand the mechanisms of HIV infection and the body's immune response) is used in conjunction with CD4 to invade target cells.

It is conceivable that the CXCR6 gene polymorphism (rs2234358) plays a potential role in the virological treatment response, with the T allele having a protective effect. This could explain the higher treatment success rate in Egyptian HCV patients (Hassona MM et alk. 2021).

The 3p21.31 gene cluster has also been identified as a genetic susceptibility locus in patients with Covid-19 and respiratory failure, with possible involvement of the ABO blood group system (Severe Covid-19 GWAS Group et al. 2020).

Diseases associated with CXCR6 include immunodeficiency diseases and "androgen insensitivity syndrome" (Androgen insensitivity syndrome/AIS is an X-linked recessive disorder that affects sexual development in individuals with a 46,XY karyotype. It results in female external genitalia, female breast development, blind vagina, absent uterus and abdominal or inguinal testes. There are three forms of AIS: complete, partial and mild. Complete AIS has typical female external genitalia, while partial AIS can have predominantly female, predominantly male or ambiguous external genitalia. Mild AIS has typical male external genitalia. AIS is caused by genetic changes in the AR gene (androgen receptor 2 gene) and is inherited in an X-linked recessive manner.)

1. Hassona MM et alk. (2021) Chemokine receptor CXCR6 gene polymorphism and treatment response of chronic hepatitis C virus in Egyptian patients. Clin Exp Hepatol 7:370-376.
2. Korbecki J et al. (2021) The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature. Int J Mol Sci 22:843.
3. Severe Covid-19 GWAS Group et al (2020) Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med 383:1522-1534.