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Blood, 15 January 2005, Vol. 105, No. 2, pp. 742-749.
Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-05-1891.


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IMMUNOBIOLOGY

Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo

Kristen M. Kerksiek, Florence Niedergang, Philippe Chavrier, Dirk H. Busch, and Thomas Brocker

From the Institute for Immunology, Ludwig-Maximilians University, Munich, Germany; Membrane and Cytoskeleton Dynamics Group, Institut Curie, Centre National de la Recherche Scientifique UMR-144, Paris, France; and Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.

To better understand the influence of cytoskeletal regulation on dendritic cell (DC) function in vivo, the Rho guanosine triphosphatase (GTPase) Rac1 was selectively inhibited in DCs in transgenic (Tg) mice. Although transgene expression did not interfere with the migratory capacities of DC in vivo, a decreased uptake of fluorescent probes was observed. Interestingly, the absence of full Rac1 function most strongly affected the development and function of CD8+ DCs. Apoptotic cell uptake was severely reduced in Tg mice, impairing subsequent DC-mediated cross-presentation and priming of bacteria-specific T-cell responses. These findings highlight a special role for Rac1 in the capacity of CD8+ DCs to endocytose apoptotic cells and prime T cells via cross-presentation.


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Dendritic cells thrive on Rac1
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