An Overview of FcγRIIb Mediated HIV and Small Immune Complex Clearance Function of Liver Sinusoidal Endothelial Cells: A Pathway for New Immunotherapies

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The Ohio State University

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The effect of Fc receptors on the regulation of the immune system is well known. In recent years, the so called “inhibitory receptor” FcγRIIb has been shown to be responsible for the clearance mechanism of the liver endothelium, such as clearance of viruses, bacteria, and small immune complexes (SIC). To model the mechanism of clearance via FcγRIIb, antibody-opsonized HIV-like particles (Ab-HIV) were used. It was found that Ab-VLP were cleared considerably faster from circulation than VLP by FcγRIIb on LSEC and the effector mechanism of LSEC FcγRIIb was identified to be endocytosis. From these results, pathological small immune complexes which lead to autoimmune disorders were then studied. A standard treatment for many autoimmune disorders such as Systemic Lupus Erythematosus (SLE), glomerulonephritis, and Idiopathic Thrombocytopenic Purpura (ITP) is intravenous immunoglobulin G (IVIG), however its mechanism is largely unknown. Due to its efficacy and the role FcγRIIb in clearance of SIC, it was hypothesized that the mechanism of IVIG is through the function of the FcγRIIb receptor in order to further understand it in order to further its efficacy for future immunotherapies to treat autoimmune disorders. The effect of IVIG on isolated LSEC from humanized 2B-KIX mice showed an upregulation in the expression of FcγRIIb on the cells surface. Thus, it is clear that the mechanism of action of IVIG on the clearance of SIC from circulation is through the upregulation of FcγRIIb. Modulation of this receptor could lead to new immunotherapies that can more effectively clear HIV and SICs and be a treatment for many other autoimmune disorders.