Current in vivo immune checkpoint receptor therapies in rheumatic diseases. T-cell activation requires two signals. The first is via the T-cell receptor (TCR), where peptide is presented by the major histocompatibility complex (MHC) on responder cells. The second involves a network of co-inhibitory and co-stimulatory molecules pathways such as CD80/CD86-CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4), inducible co-stimulator (ICOS)-ICOS ligand (ICOSL), programmed death-1 (PD-1), programme death ligand-1/2 (PD-L1/PD-L2), 4-1BB-4-1BB ligand (4-1BBL), CD40-CD154 ligand, OX40-OX40 ligand and CD27-CD70. This diagram summarizes current therapies for manipulating these pathways to suppress disease in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), psoriasis (Ps), and systemic sclerosis (SSc). Ab, antibody; CTX, cyclophosphamide; JIA, juvenile idiopathic arthritis.