| First Author | Karsten CM | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 9 | Pages | 1401-6 |
| PubMed ID | 22922409 | Mgi Jnum | J:192766 |
| Mgi Id | MGI:5466456 | Doi | 10.1038/nm.2862 |
| Citation | Karsten CM, et al. (2012) Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcgammaRIIB and dectin-1. Nat Med 18(9):1401-6 |
| abstractText | Complement is an ancient danger-sensing system that contributes to host defense, immune surveillance and homeostasis. C5a and its G protein-coupled receptor mediate many of the proinflammatory properties of complement. Despite the key role of C5a in allergic asthma, autoimmune arthritis, sepsis and cancer, knowledge about its regulation is limited. Here we demonstrate that IgG1 immune complexes (ICs), the inhibitory IgG receptor FcgammaRIIB and the C-type lectin-like receptor dectin-1 suppress C5a receptor (C5aR) functions. IgG1 ICs promote the association of FcgammaRIIB with dectin-1, resulting in phosphorylation of Src homology 2 domain-containing inositol phosphatase (SHIP) downstream of FcgammaRIIB and spleen tyrosine kinase downstream of dectin-1. This pathway blocks C5aR-mediated ERK1/2 phosphorylation, C5a effector functions in vitro and C5a-dependent inflammatory responses in vivo, including peritonitis and skin blisters in experimental epidermolysis bullosa acquisita. Notably, high galactosylation of IgG N-glycans is crucial for this inhibitory property of IgG1 ICs, as it promotes the association between FcgammaRIIB and dectin-1. Thus, galactosylated IgG1 and FcgammaRIIB exert anti-inflammatory properties beyond their impact on activating FcgammaRs. |
