FcγRIIb inhibits immune complex-induced VEGF-A production and intranodal lymphangiogenesis

Abstract

Significance 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.

Signal Factors Secreted by 2D and Spheroid Mesenchymal Stem Cells and by Cocultures of Mesenchymal Stem Cells Derived Microvesicles and Retinal Photoreceptor Neurons

“…MCP-3 can attract macrophages during inflammation and metastasis and augments monocyte antitumor activity [ 47 ]. VEGF are known to promote vasculogenesis and angiogenesis and can also contribute to inflammation by promoting lymphangiogenesis [ 48 , 49 ]. TGF β 3 are involved in cell differentiation and cell survival [ 50 ] and it was shown that the hypoxic environment inside MSC spheroids promoted TGF β 3 expression, leading to enhanced chondrogenic differentiation of MSCs and cartilage formation [ 51 ].…”

FcγRIIB and autoimmunity

“…Monocyte‐derived macrophages from subjects with the FCGR2B T/T232 genotype showed increased FcγR‐mediated VEGF‐A production, demonstrating that a similar process is likely to occur in humans. Thus, IgG immune complexes contribute to inflammation through VEGF‐A‐driven lymph node lymphangiogenesis, which is controlled by FcγRIIB .…”

Fcγ Receptors in Solid Organ Transplantation

“…IgG immune complexes can induce VEGF-A production by macrophages, driving lymphangiogenesis in vivo, and represents another potential mechanism by which DSA might impact allograft rejection [74].

Transcriptomic signatures in ABMR — FCGR3A transcripts are enriched within renal transplant biopsies, and correlate with the presence of DSA and ABMR.

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