In contrast to PD-1/PD-L1 and CTLA-4, where agonistic approaches have therapeutic benefit, blockade of ICOS or its ligand (ICOSL) reduces disease severity in murine models of rheumatoid arthritis, such as the glucose-6-phosphate isomerase (GPI)-induced arthritis model [51]. The gene discussed is ICOS; the disease is rheumatoid arthritis.