Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo.
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.
Kerksiek
Kristen M
KM
Institute for Immunology, Ludwig-Maximilians University, Munich, Germany.
Niedergang
Florence
F
Chavrier
Philippe
P
Busch
Dirk H
DH
Brocker
Thomas
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D008088:Listeriosis / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*
D039521:CD11c Antigen; D016827:CD8 Antigens; D020830:rac1 GTP-Binding Protein