Siglec-H, or sialic acid binding immunoglobulin-like lectin H, is a CD33 related protein expressed specifically by plasmacytoid dendritic cells or pDCs (1, 2). Antigen-mediated delivery by Siglec-H in pDCs inhibits Th cell proliferation and further antibody responses. This leads to lessened expansion and Th1/Th17 polarization (3). Constant and low density antigen presentation by Siglec-H is thought to lead to an exhaustive type lessening of the response in CD4+ cells but not tolerance. A number of pathways have been proposed for the Siglec-H induced T cell hyporesponsiveness. Ever decreasing activation cycles in the presence of low level but continuous antigen delivery, as that observed with Siglec-H, have also been demonstrated to impart FoxP3+ Tregs immunosuppressive tolerogen-like effects (4, 5). Ability to identify and control Siglec-H antigen mediated delivery activities with specific antibody provides a focal point for potential development of inflammation controls.
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4. Zhang J et al 2006 Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107: 3600-3608.
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7. Kang HK et al 2007 Low-Dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and control of inflammatory Th17cells. J. Immunol 178: 7849-7855.
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