Immunoglobulin G-dependent inhibition of inflammatory bone remodeling requires pattern recognition receptor Dectin-1

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

Journal

Immunity Elsevier

Book Volume: 56

Pages Range: 1046-1063.e7

Journal Issue: 5

DOI: 10.1016/j.immuni.2023.02.019

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.

Authors with CRIS profile

Michaela Seeling Lehrstuhl für Genetik Matthias Pöhnl Professur für Computational Biology Sibel Kara-Kocak Lehrstuhl für Genetik Nathalie Horstmann Lehrstuhl für Genetik Carolina Daniela Riemer Lehrstuhl für Genetik Miriam Wöhner Professur für Genetik Christin Brückner Lehrstuhl für Genetik Anja Werner Lehrstuhl für Genetik Markus Biburger Lehrstuhl für Genetik Leon Altmann Lehrstuhl für Genetik Lukas Amon Department of Dermatology Christian Lehmann Department of Dermatology Meik Kunz Lehrstuhl für Medizinische Informatik Diana Dudziak Professur für die Biologie Dendritischer Zellen Georg Schett Lehrstuhl für Innere Medizin III Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Anja Lux Lehrstuhl für Genetik Rainer Böckmann Professur für Computational Biology Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universität Ulm DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE)

How to cite

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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