期刊
IMMUNITY
卷 30, 期 4, 页码 544-555出版社
CELL PRESS
DOI: 10.1016/j.immuni.2009.01.013
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资金
- Institut National de la Sainte et de la Recherche Medicale (INSERM)
- Ligue National de Lutte contre le Cancer (LLNC)
- Institut Curie
- Contrat CEE DC-Thera [LSBH-CT-2004-512074, LSHC-CT-2006-518234]
- Fondation Bettencourt and Association de Recherche contre le Cancer
- Fundacao, Luso-Americana para o Desenvolvimento and Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-MII/69280/2006, PTDC/SAU-MII/78333/2006]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-MII/69280/2006, PTDC/SAU-MII/78333/2006] Funding Source: FCT
A unique subpopulation of spleen dendritic cells (DCs) that express the CD8 surface marker efficiently present phagocytosed antigens to CD8(+) T lymphocytes in a process called crosspresentation, which initiates cytotoxic immune responses. We now show that the small GTPase Rac2 plays a critical role in antigen crosspresentation selectively in this DC subpopulation. In CD8(+) DCs, Rac2 determines the subcellular assembly of the NADPH oxidase complex (NOX2) to phagosomes, whereas in CD8(-) DCs, Rac1 mediates the assembly of NOX2 at the plasma membrane. In the absence of Rac2, the production of reactive oxygen species (ROS) in DC-phagosomes was abolished, the phagosomal pH dropped, and the efficiency of antigen crosspresentation was reduced. We conclude that the activity of Racl and 2 control crosspresentation in DC subpopulations through the regulation of phagosomal oxidation and pH.
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