Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models.
Expression of inflammatory cytokines is augmented in the joints of patients with rheumatoid arthritis (RA). We found that cytokine levels are also elevated in the joints of a mouse arthritis model, human T-cell leukemia virus type I (HTLV-I) transgenic (Tg) mouse. Depletion of IL-1 by gene targeting greatly reduced the incidence of the disease, indicating the importance of this cytokine in the development of arthritis. Furthermore, IL-1 receptor antagonist (IL-1Ra)-deficient mice develop autoimmunity and arthritis spontaneously. These observations suggest that excess IL-1 signaling the causes autoimmunity. We show that IL-1 activates the immune system non-specifically by inducing CD40L and OX40 co-signaling molecules on T cells. In this review, the roles of IL-1 in the development of autoimmunity and arthritis in mouse models will be discussed.
Iwakura
Yoichiro
Y
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. iwakura@ims.u-tokyo.ac.jp
D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000821:virology; D001169:Arthritis, Experimental / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics; D003433:Crosses, Genetic; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D018390:Gene Targeting; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018448:Models, Immunological; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000235:genetics; D048069:Tumor Necrosis Factors
D001323:Autoantibodies; D019013:CD40 Antigens; D016207:Cytokines; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors; D023201:CD40 Ligand