title: Immune checkpoint receptors in regulating immune reactivity in rheumatic disease.
abstract: Immune checkpoint regulators are critical modulators of the immune system, allowing the initiation of a productive immune response and preventing the onset of autoimmunity. Co-inhibitory and co-stimulatory immune checkpoint receptors are required for full T-cell activation and effector functions such as the production of cytokines. In autoimmune rheumatic diseases, impaired tolerance leads to the development of diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome. Targeting the pathways of the inhibitory immune checkpoint molecules CD152 (cytotoxic T lymphocyte antigen-4) and CD279 (programmed death-1) in cancer shows robust anti-tumor responses and tumor regression. This observation suggests that, in autoimmune diseases, the converse strategy of engaging these molecules may alleviate inflammation owing to the success of abatacept (CD152-Ig) in rheumatoid arthritis patients. We review the preclinical and clinical developments in targeting immune checkpoint regulators in rheumatic disease.
authors.affiliation: Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, Lebanon, NH  03756, USA. sabrina.c.delong@dartmouth.edu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ceeraz
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Nowak
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Burns
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D018501:Antirheumatic Agents / Q000276:immunology / Q000627:therapeutic use; D061025:Costimulatory and Inhibitory T-Cell Receptors / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D061025:Costimulatory and Inhibitory T-Cell Receptors; D011948:Receptors, Antigen, T-Cell