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Blood, 1 August 2006, Vol. 108, No. 3, pp. 947-955.
Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2005-12-4812.


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IMMUNOBIOLOGY

The apoptotic-cell receptor CR3, but not {alpha}vbeta5, is a regulator of human dendritic-cell immunostimulatory function

Mojca Skoberne, Selin Somersan, Wanda Almodovar, Tuan Truong, Kseniya Petrova, Peter M. Henson, and Nina Bhardwaj

From the New York University School of Medicine, New York; and Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO.

Dendritic cells (DCs) that capture apoptotic cells (ACs) in the steady state mediate peripheral tolerance to self-antigens. ACs are recognized by an array of receptors on DCs, the redundancy of which is not completely defined. We made use of an AC surrogate system to address the individual roles of the {alpha}vbeta5 and complement receptors (CRs) in the phagocytosis and induction of immunity. CR3 and CR4, while substantially less efficient than {alpha}vbeta5 in internalizing ACs, initiate signals that render DCs tolerogenic. Responding T cells show impaired proliferation and IFN{gamma} production and subsequently die by apoptosis. While tolerogenic DCs are not induced via {alpha}vbeta5, coligation of CR3 and {alpha}vbeta5 maintains the DC's tolerogenic profile. This immunomodulatory role, however, is countered by a significant inflammatory stimulus such as bacterial infection. Overall, our data suggest that under steady-state conditions, signaling via CRs predominates to render DCs tolerogenic.


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