ICOSLG Gene

The ICOSLG gene (ICOSLG stands for Inducible T Cell Costimulator Ligand) is a protein coding gene located on chromosome 21q22.3. The encoded protein is the ligand for the T cell-specific cell surface receptor ICOS. The protein is expressed in both lymphoid and non-lymphoid tissues and is an important molecule for upregulating and promoting T cell immune responses. It acts as a costimulatory signal for T cell proliferation and cytokine secretion and induces B cell proliferation and differentiation into plasma cells. Induced expression of ICOS on activated T cells mainly regulates the secretion of Th2 cytokines, thereby shifting the immune response toward the Th2 type. Expression of ICOSLG in naive B cells and monocytes is low.

The ICOS/ICOSLG pathway is thought to be involved in immunopathogenesis, such as infections, alergic reactions, autoimmune diseases, transplantation immunity, and tumor immunity. ICOSLG is also an important costimulator in endothelial cell-mediated T cell activation. ICOSLG plays an important physiological role in the reactivation of effector/memory T cells on endothelium and controls the entry of immune cells into inflamed tissues.

Diseases associated with ICOSLG include autoimmune diseases of the exocrine system and autoimmune diseases of the musculoskeletal system.

Mutations in the ICOSLG gene lead to a defect in the formation of antibodies and memory B cells. Mutant ICOSLG also impaired the migration of lymphocytes and neutrophil granulocytes by endothelial cells, which normally express ICOSLG (Dubois PC et al. 2010). Autosomal recessive mutations of ICOSLG in humans result in a combined immunodeficiency syndrome characterized primarily by recurrent respiratory infections and significant disease caused by DNA-based viruses at epithelial barriers, including human papillomavirus (HPV). These features also occur in individuals with loss of function of the complementary gene, ICOS (Roussel L et al. 2021).

1. Dubois PC et al (2010) Multiple common variants for celiac disease influencing immune gene expression. Nat Genet 42:295-302.
2. Roussel L et al (2021) ICOSL in host defense at epithelial barriers: lessons from ICOSLG deficiency. Curr Opin Immunol 72:21-26.