Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy.
Chronic diseases, such as periodontal disease (PD) and rheumatoid arthritis (RA), are characterized by a robust immune response resulting in unresolved inflammation. Inflammation is mediated by proinflammatory cytokines; recently, a novel subset of T-helper (Th) cells was identified that plays a crucial role in inflammation and autoimmune disease. This population secretes several proinflammatory cytokines, including the novel cytokine interleukin (IL)-17, and, hence, has been termed "Th17." Inflammatory cytokines are implicated in the progression of localized chronic infections, such as PD, and in serious systemic pathologies, such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease. IL-17 mediates inflammation through a receptor (IL-17R) composed of two subunits, IL-17RA and IL-17RC. Drugs that antagonize inflammatory cytokines are used therapeutically to downregulate immune-mediated pathology in conditions such as RA, although not all patients respond well to this approach. Therefore, identification of potential novel therapeutic targets, such as the IL-17 signaling complex, may be clinically relevant for mitigating inflammatory pathology. However, the manner in which such a therapeutic may influence the onset and progression of PD is poorly understood. Therapeutics that antagonize inflammatory cytokines ameliorate inflammation and bone loss and may have broader implications for individuals with systemic diseases in which inflammation and autoimmunity predominate.
Kramer
Jill M
JM
Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14212, USA.
Gaffen
Sarah L
SL
D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D008336:Mandibular Diseases / Q000276:immunology / Q000382:microbiology; D008439:Maxillary Diseases / Q000276:immunology / Q000382:microbiology; D051379:Mice; D053244:Osteoprotegerin / Q000276:immunology; D010510:Periodontal Diseases / Q000276:immunology / Q000382:microbiology; D053245:RANK Ligand / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D020381:Interleukin-17; D053244:Osteoprotegerin; D053245:RANK Ligand; D053722:Receptors, Interleukin-17