The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis

Royzman D, Andreev D, Stich L, Peckert K, Wild A, Zinser E, Mühl-Zürbes P, Jones E, Adam S, Frey S, Fuchs M, Kunz M, Bäuerle T, Nagel L, Schett G, Bozec A, Steinkasserer A (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 13

DOI: 10.3389/fimmu.2022.936995

Abstract

Here we show that soluble CD83 induces the resolution of inflammation in an antigen-induced arthritis (AIA) model. Joint swelling and the arthritis-related expression levels of IL-1 beta, IL-6, RANKL, MMP9, and OC-Stamp were strongly reduced, while Foxp3 was induced. In addition, we observed a significant inhibition of TRAP(+) osteoclast formation, correlating with the reduced arthritic disease score. In contrast, cell-specific deletion of CD83 in human and murine precursor cells resulted in an enhanced formation of mature osteoclasts. RNA sequencing analyses, comparing sCD83- with mock treated cells, revealed a strong downregulation of osteoclastogenic factors, such as Oc-Stamp, Mmp9 and Nfatc1, Ctsk, and Trap. Concomitantly, transcripts typical for pro-resolving macrophages, e.g., Mrc1/2, Marco, Klf4, and Mertk, were upregulated. Interestingly, members of the metallothionein (MT) family, which have been associated with a reduced arthritic disease severity, were also highly induced by sCD83 in samples derived from RA patients. Finally, we elucidated the sCD83-induced signaling cascade downstream to its binding to the Toll-like receptor 4/(TLR4/MD2) receptor complex using CRISPR/Cas9-induced knockdowns of TLR4/MyD88/TRIF and MTs, revealing that sCD83 acts via the TRIF-signaling cascade. In conclusion, sCD83 represents a promising therapeutic approach to induce the resolution of inflammation and to prevent bone erosion in autoimmune arthritis.

Authors with CRIS profile

Dmytro Royzman Department of Immune Modulation Darja Andreev Department of Medicine 3 – Rheumatology and Immunology Andreas Wild Lehrstuhl für Biochemie und Molekulare Medizin Elisabeth Zinser Medizinische Fakultät Susanne Adam Department of Medicine 3 – Rheumatology and Immunology Silke Frey Department of Medicine 3 – Rheumatology and Immunology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Juniorprofessur für Osteoimmunologie Alexander Steinkasserer Professur für Experimentelle Dermatologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

A089: CD83 as a key regulator during immune homeostasis and neuroinflammation July 1, 2020 - June 30, 2023

Involved external institutions

Fraunhofer-Institut für Toxikologie und Experimentelle Medizin (ITEM) / Fraunhofer Institute for Toxicology and Experimental Medicine DE Germany (DE)

How to cite

APA:

Royzman, D., Andreev, D., Stich, L., Peckert, K., Wild, A., Zinser, E.,... Steinkasserer, A. (2022). The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis. Frontiers in Immunology, 13. https://dx.doi.org/10.3389/fimmu.2022.936995

MLA:

Royzman, Dmytro, et al. "The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis." Frontiers in Immunology 13 (2022).

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