Seeling M, Pöhnl M, Kara S, Horstmann N, Riemer CD, Wöhner M, Liang C, Brückner C, Eiring P, Werner A, Biburger M, Altmann L, Schneider M, Amon L, Lehmann C, Lee S, Kunz M, Dudziak D, Schett G, Bäuerle T, Lux A, Tuckermann J, Vögtle T, Nieswandt B, Sauer M, Böckmann R, Nimmerjahn F (2023)
Publication Type: Journal article, Original article
Publication year: 2023
Book Volume: 56
Pages Range: 1046-1063.e7
Journal Issue: 5
DOI: 10.1016/j.immuni.2023.02.019
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.
APA:
Seeling, M., Pöhnl, M., Kara, S., Horstmann, N., Riemer, C.D., Wöhner, M.,... Nimmerjahn, F. (2023). Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1. Immunity, 56(5), 1046-1063.e7. https://doi.org/10.1016/j.immuni.2023.02.019
MLA:
Seeling, Michaela, et al. "Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1." Immunity 56.5 (2023): 1046-1063.e7.
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