Anti-FCGR2B monoclonal antibody, clone 200804 [Biotin]

Signaling through stimulator of interferon genes (STING) leads to the production of type I interferons (IFN-Is) and inflammatory cytokines. A gain-of-function mutation in STING was identified in an autoinflammatory disease (STING-associated vasculopathy with onset in infancy; SAVI). The expression of cyclic GMP-AMP, DNA-activated cGAS-STING pathway, increased in a proportion of patients with SLE. The STING signaling pathway may be a candidate for targeted therapy in SLE. Here, we demonstrated that disruption of STING signaling. ameliorated lupus development in Fcgr2b-deficient mice. Actixation of STING promoted maturation of conventional dendritic cells and differentiation of plasmacytoid dendritic cells via LYN interaction and phosphorylalon. The inhibition of LYN decreased the differentiation of STING-activated dendritic cells. Adoptive transfer of STING-activated bone marrow-derived dendritic cells into the CGR2B and STING double-deficiency mice restored lupus phenotypes. These findings provide evidence that the inhibition of STING signaling may be a candidate targeted treatment for a subset of patients with SLE.

The autoimmune-type Fcgr2b with deletion polymorphism in AP-4-binding site in the promoter region is suggested to be one most plausible susceptibility gene for systemic lupus erythematosus (SLE). We previously found that there is a strong epistatic interaction between the autoimmune-type Fcgr2b polymorphism and Y chromosome-linked autoimmune acceleration (Yaa) mutation, thus severe SLE observed in BXSB males neither develops in BXSB females nor in the congenic BXSB.IIBB6 males carrying wild C57BL/6-type Fcgr2b. Present studies examined whether the wild-type Fcgr2b could suppress SLE in mice carrying Yaa-unrelated SLE susceptibility genes. Comparison of disease features between SLE-prone (NZW x BXSB) F1 females and the congenic (NZW x BXSB.IIBB6) F1 females carrying wild-type Fcgr2b showed that, as compared with findings in the former, SLE features including activation/proliferation of not only B cells but also T cells and monocytes/macrophages were all inhibited in the latter. It was concluded that the autoimmune-type Fcgr2b promotes and the wild-type inhibits SLE through mechanisms that promote and suppress activation/proliferation of a wide variety of immune cells, respectively. Thus, the Fcgr2b polymorphism is a key genetic element for not only Yaa-related but also Yaa-unrelated lupus. (C) 2009 Elsevier Ltd. All rights reserved.