We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis.
- Authors
Royzman, Dmytro; Andreev, Darja; Stich, Lena; Peckert-Maier, Katrin; Wild, Andreas B.; Zinser, Elisabeth; Mühl-Zürbes, Petra; Jones, Evan; Adam, Susanne; Frey, Silke; Fuchs, Maximilian; Kunz, Meik; Bäuerle, Tobias; Nagel, Lisa; Schett, Georg; Bozec, Aline; Steinkasserer, Alexander
- 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-1β, 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.
- Subjects
OSTEOCLASTS; JOINT diseases; ARTHRITIS; OSTEOCLAST inhibition; TOLL-like receptors; INFLAMMATION
- Publication
Frontiers in Immunology, 2022, Vol 13, p01
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.936995