Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1
Year: 2023
Type: article
Abstract: Immunoglobulin G (IgG) antibodies are major drivers of inflammation during infectious and autoimmune diseases. In pooled serum IgG (IVIg), however, antibodies have a potent immunomodulatory and anti-inflammatory activity, but how this is mediated is unclear. We studied IgG-dependent initiation of resolution of inflammation in cytokine- and autoantibody-driven models of rheumatoid arthritis and found IVIg sialylation inhibited joint inflammation, whereas inhibition of osteoclastogenesis was sialic acid independent. Instead, IVIg-dependent inhibition of osteoclastogenesis was abrogated in mice lacking receptors Dectin-1 or FcγRIIb. Atomistic molecular dynamics simulations and super-resolution microscopy revealed that Dectin-1 promoted FcγRIIb membrane conformations that allowed productive IgG binding and enhanced interactions with mouse and human IgG subclasses. IVIg reprogrammed monocytes via FcγRIIb-dependent signaling that required Dectin-1. Our data identify a pathogen-independent function of Dectin-1 as a co-inhibitory checkpoint for IgG-dependent inhibition of mouse and human osteoclastogenesis. These findings may have implications for therapeutic targeting of autoantibody and cytokine-driven inflammation.
Source: Immunity
Authors: Michaela Seeling, Matthias Pöhnl, Sibel Kara, Nathalie Horstmann, Carolina Riemer, Miriam Wöhner, Chunguang Liang, Christin Brückner, Patrick Eiring, Anja Werner, Markus Biburger, Leon Altmann, Martin Schneider, Lukas Amon, Christian H.K. Lehmann, Sooyeon Lee, Meik Kunz, Diana Dudziak, Georg Schett, Tobias Bäuerle, Anja Lux, Jan Tuckermann, Timo Vögtle, Bernhardt Nieswandt, Markus Sauer, Rainer A. Böckmann, Falk Nimmerjahn
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,080
OpenAlex ID: W4328088997