FcγRIIb inhibits immune complex-induced VEGF-A production and intranodal lymphangiogenesis
Abstract
Antibody (IgG) plays an important role in defense against infection and in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Low affinity-activating fragment crystallizable gamma receptors (FcγRs) that bind IgG immune complexes (ICs) mediate many effector functions of antibody and are controlled by an inhibitory receptor, FcγRIIb. Here we show a previously unappreciated role for IC in driving an expansion of lymphatic conduits within lymph nodes. This was dependent on macrophage VEGF-A production and inhibited by FcγRIIb. Lymphangiogenesis and VEGF-A were increased in the lymph nodes of mice with arthritis and SLE and in macrophages obtained from people with a SLE-associated, defunctioning polymorphism in FCGR2B. These findings have implications for the pathogenesis and treatment of autoimmune diseases.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2014
- DOI:
- 10.1073/pnas.1413915111
- Bibcode:
- 2014PNAS..11117971C