Dendritic cells

Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blasius, A. L. et al. Blood 17 Nov 2005 (doi:10.1182/blood-2005-09-3746)

Marco Colonna and colleagues previously generated an antibody (denoted 440c) specific for interferon (IFN)-producing cells (IPCs; also known as plasmacytoid dendritic cells). They now show that 440c binds a new member of the sialic-acid-binding immunoglobulin-like lectin (SIGLEC) family, SIGLEC-H. SIGLEC-H is unique because it binds the adaptor protein DAP12 (DNAX activation protein 12). Stimulation with 440c has been shown to inhibit IPC production of IFNα that is induced by CpG-containing DNA (a Toll-like receptor 9 (TLR9) ligand), and low concentrations of CpG-containing DNA induce DAP12-deficient IPCs to produce more IFNα than wild-type cells. But high concentrations of CpG-containing DNA induce equivalent amounts of IFNα, leading the authors to suggest that low-level activation of DAP12 for example, by antibodies specific for associated receptors, sequesters signalling molecules and interferes with TLR signalling.

Phagocytosis

A role for mammalian Diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Colucci-Guyon, E. et al. Curr. Biol. 15, 2007–2012 (2005)

Phagocytosis is mediated by receptors such as Fc receptors (FcRs) and complement receptor 3 (CR3). Colucci-Guyon et al. show that Diaphanous homologue 1 (DIA1), which regulates actin remodelling in fibroblasts, colocalizes with polymerized actin at the site of CR3-mediated phagocytosis in the macrophage cell line RAW264.7. In RAW264.7 cells, mutated DIA2 proteins that can inhibit endogenous DIA1 and DIA2, as well as knockdown of Dia1 expression by small interfering RNA, decreased CR3-mediated phagocytosis, but had no effect on FcR-mediated phagocytosis. In addition, both the DIA2 mutants and knockdown of Dia1 expression decreased actin recruitment to the site of CR3-mediated phagocytosis, providing a molecular distinction between CR3- and FcR-mediated phagocytosis.

Autoimmunity

Identification of autoantibody clusters that best predict lupus disease activity using glomerular proteome arrays. Zhen, Q. L. et al. J. Clin. Invest. 115, 3428–3439 (2005)

Systemic lupus erythematosus (SLE) is characterized by circulating autoantibodies, in particular autoantibodies specific for DNA or the glomerulus. Zhen et al. developed a 'glomerular-proteome array' to analyse the fine specificity of these autoantibodies and screened numerous glomerular, glomerular basement membrane and DNA antigens using this approach. IgG in the sera of patients with SLE fell into five clusters of antigen reactivity, two of which were associated with higher disease activity. By contrast, the specificity of IgM autoantibodies fell into two clusters of antigen reactivity (DNA-reactive or seemingly polyreactive). Individuals with IgM in the DNA-reactive cluster had more severe disease, leading the authors to suggest that analysing autoantibody specificity on a glomerular-proteome array might provide a new means of screening patients with SLE.