title: (p40)2-Fc reduces immune-inflammatory response through the activation of T cells in collagen induced arthritis mice.
abstract: IL-12p40 homodimer, a natural antagonist of IL-12 and IL-23, performs an important role in the expression of proinflammatory cytokines that is essential for Th1 and Th17 immune responses. Here, we reveal the therapeutic and immunosuppressive effect of the IL-12p40 subunit ((p40)2-Fc) in an experimental autoimmune arthritis model. We hypothesized that (p40)2-Fc may reduce the inflammatory response and the activation of T cells. In this study, we intraperitoneally injected (p40)2-Fc into collagen induced arthritis (CIA) mice to identify whether (p40)2-Fc attenuates CIA severity. (p40)2-Fc reduced the development of CIA, joint inflammation and cartilage destruction. (p40)2-Fc also significantly decreased the concentration of serum immunoglobulin as well as the number of T cells and C II specific T cells. In addition, osteoclastogenesis in (p40)2-Fc treated mice was down-regulated compared to the mice treated with (p40)2-Fc control. We observed that (p40)2-Fc treatment alleviates arthritis in mice with CIA, reducing inflammation and osteoclast differentiation. These findings suggest that (p40)2-Fc can be a potential therapeutic approach for autoimmune arthritis.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Research Center, Hanmi Pharm. Co. Ltd., Gyeonggi-do, South Korea.
authors.forename: Seong-Jeong
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Research Center for Viral Infectious Diseases and Control, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea.
authors.forename: Doo-Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: NeoImmuneTech, Rockville, MD, 20850, USA.
authors.forename: Se-Hwan
authors.initials: SH
authors.lastname: Yang
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: Integrative Bioscience and Biotechnology, World Class University, Pohang University of Science and Technology Biotechnology Center, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Sung
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, South Korea. Electronic address: iammila@catholic.ac.kr.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D053762:Interleukin-12 Subunit p40 / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010012:Osteogenesis / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D007141:Immunoglobulin Fc Fragments; D053762:Interleukin-12 Subunit p40
keywords: (p40)2-Fc; Osteoclastogenesis; Rheumatoid arthritis