Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner
Royzman D, Andrev D, Stich L, Rauh M, Bäuerle T, Ellmann S, Boon L, Kindermann M, Peckert K, Bozec A, Schett G, Steinkasserer A, Zinser E (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 10
Abstract
Interference with autoimmune-mediated cytokine production is a key yet poorly developed approach to treat autoimmune and inflammatory diseases such as rheumatoid arthritis. Herein, we show that soluble CD83 (sCD83) enhances the resolution of autoimmune antigen-induced arthritis (AIA) by strongly reducing the expression levels of cytokines such as IL-17A, IFN gamma, IL-6, and TNF alpha within the joints. Noteworthy, also the expression of RANKL, osteoclast differentiation, and joint destruction was significantly inhibited by sCD83. In addition, osteoclasts which were cultured in the presence of synovial T cells, derived from sCD83 treated AIA mice, showed a strongly reduced number of multinuclear large osteoclasts compared to mock controls. Enhanced resolution of arthritis by sCD83 was mechanistically based on IDO, since inhibition of IDO by 1-methyltryptophan completely abrogated sCD83 effects on AIA. Blocking experiments, using anti-TGF-beta antibodies further revealed that also TGF-beta is mechanistically involved in the sCD83 induced reduction of bone destruction and cartilage damage as well as enhanced resolution of inflammation. Resolution of arthritis was associated with increased numbers of regulatory T cells, which are induced in a sCD83-IDO-TGF-beta dependent manner. Taken together, sCD83 represents an interesting approach for downregulating cytokine production, inducing regulatory T cells and inducing resolution of autoimmune arthritis.
Authors with CRIS profile
Dmytro Royzman
Department of Immune Modulation
Manfred Rauh
Department of Paediatrics and Adolescent Medicine
Tobias Bäuerle
Professur für Multimodale Bildgebung in der präklinischen Forschung
Stephan Ellmann
Institute of Radiology
Aline Bozec
Juniorprofessur für Osteoimmunologie
Georg Schett
Lehrstuhl für Innere Medizin III
Alexander Steinkasserer
Professur für Experimentelle Dermatologie
Involved external institutions
Netherlands (NL)How to cite
APA:
Royzman, D., Andrev, D., Stich, L., Rauh, M., Bäuerle, T., Ellmann, S.,... Zinser, E. (2019). Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner. Frontiers in Immunology, 10. https://dx.doi.org/10.3389/fimmu.2019.00633
MLA:
Royzman, Dmytro, et al. "Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner." Frontiers in Immunology 10 (2019).
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