Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner

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Details zur Publikation

Autor(en): 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
Zeitschrift: Frontiers in Immunology
Jahr der Veröffentlichung: 2019
Band: 10
ISSN: 1664-3224


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.


FAU-Autoren / FAU-Herausgeber

Bäuerle, Tobias Prof. Dr.
Professur für Multimodale Bildgebung in der präklinischen Forschung
Bozec, Aline Prof. Dr.
Juniorprofessur für Osteoimmunologie
Ellmann, Stephan Dr. med.
Radiologisches Institut
Rauh, Manfred Prof. Dr.
Kinder- und Jugendklinik
Royzman, Dmytro
Immunmodulatorische Abteilung in der Hautklinik
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Steinkasserer, Alexander Prof. Dr.
Professur für Experimentelle Dermatologie


Autor(en) der externen Einrichtung(en)
Bioceros Holding B.V.


Zitierweisen

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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Zuletzt aktualisiert 2019-17-04 um 08:38