The ICOSLG (Inducible T-cell Costimulator Ligand), also known as ICOSL or CD275. is a member of the B7 family of costimulatory molecules. It is primarily expressed on antigen-presenting cells (APCs), such as B cells, dendritic cells, and macrophages, as well as certain non-hematopoietic cells. ICOSLG binds to its receptor ICOS (CD278) on activated T cells, playing a critical role in modulating adaptive immune responses. This interaction enhances T-cell activation, differentiation, and survival, particularly influencing the function of follicular helper T cells (Tfh) and regulatory T cells (Treg).
ICOSLG-ICOS signaling is pivotal in balancing immune activation and tolerance. It promotes cytokine production (e.g., IL-10. IL-4. IL-17) and supports germinal center formation, antibody class switching, and T-cell-dependent B-cell responses. Dysregulation of this pathway is implicated in autoimmune diseases, chronic inflammation, and cancer. For instance, elevated ICOSLG expression in tumors may contribute to immunosuppressive microenvironments.
Antibodies targeting ICOSLG are being explored therapeutically to either block or enhance its signaling. In autoimmune contexts, blocking antibodies aim to inhibit pathogenic T-cell activation. Conversely, agonist antibodies may boost anti-tumor immunity by stimulating effector T cells. Clinical trials are evaluating their safety and efficacy, highlighting ICOSLG's potential as a versatile immunomodulatory target.