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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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Submitted May 19, 2004
Accepted September 3, 2004
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*
Institute for Immunology, Ludwig-Maximilians University, Munich, Germany
Membrane and Cytoskeleton Dynamics Group, Institut Curie, Paris, France
Immunology and Hygiene, Institue for Medical Microbiology, Technical University Munich, Munich, Germany
* Corresponding author; email: tbrocker{at}ifi.med.uni-muenchen.de.
In order to better understand the influence of cytoskeletal regulation on dendritic cell (DC) function in vivo, the Rho GTPase Rac1 was selectively inhibited in DC in transgenic (Tg) mice. While 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+ DC. 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+ DC to endocytose apoptotic cells and prime T cells via cross-presentation.
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