Background
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. |
Reference
1. Amanda L. Blasius, Marina Cella, Jorge Maldonado, Toshiyuki Takai, Marco Colonna. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood. 2006 March 15; 107(6): 2474–2476.
2. Apostolou, I and H von Boehmer 2004. In Vitro instruction of suppressor commitment in naïve T cells. J. Exp. Med. 199: 1401-1408.
3. 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.
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.
5. Loschko, J et al. 2011 Antigen targeting to Plasmycotid Dendritic Cells via Siglec-H inhibits Th-Cell-Independent Autoimmunity. J. Immunol 187 doi: 10-4019/jimmunol. 11 02307.
6. http://www.copewithcytokines.de/cope.cgi?key=SIGLEC-H__REFERENCES
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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9. Josh Gregorio, Stephan Meller, Curdin Conrad, Anna Di Nardo, Bernhard Homey, Antti Lauerma, Naoko Arai, Richard L. Gallo, John DiGiovanni, Michel Gilliet. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med. 2010 December 20; 207(13): 2921–2930.
10. Daniel M. Andrews, Marie J. Estcourt, Christopher E. Andoniou, Matthew E. Wikstrom, Andrea Khong, Valentina Voigt, Peter Fleming, Hyacinth Tabarias, Geoffrey R. Hill, Robbert G. van der Most, Anthony A. Scalzo, Mark J. Smyth, Mariapia A. Degli-Esposti. Innate immunity defines the capacity of antiviral T cells to limit persistent infection. J Exp Med. 2010 June 7; 207(6): 1333–1343.
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