Blockade of IL-36 Receptor Signaling Does Not Prevent from TNF-Induced Arthritis |
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| Authors: | Anja Derer Bettina Groetsch Ulrike Harre Christina B?hm Jennifer Towne Georg Schett Silke Frey Axel J. Hueber |
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| Affiliation: | 1. Department of Internal Medicine 3 and Institute for Clinical Immunology, University Hospital Erlangen, Erlangen, Germany.; 2. Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.; 3. Department of Inflammation Research, Amgen Inc., Longmont, Colorado, United States of America.; French National Centre for Scientific Research, France, |
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| Abstract: | IntroductionInterleukin (IL)-36α is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36α and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36α induces MAP-kinase and NFκB signaling in human synovial fibroblasts with subsequent expression and secretion of pro-inflammatory cytokines.MethodsTo understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36α signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL-36α was tested in murine and human osteoclast assays.ResultsDiseased mice showed an increased expression of IL-36R and IL-36α in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF-induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays.ConclusionThus we conclude that IL-36α does not affect the development of inflammatory arthritis. |
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