Baptista, Marisa A. P.Keszei, MartonOliveira, MarianaSunahara, Karen K. S.Andersson, JohnDahlberg, Carin I. M.Worth, Austen J.Liedén, AgneKuo, I-ChunWallin, Robert P. A.Snapper, ScottEidsmo, LivScheynius, AnnikaKarlsson, Mikael C. I.Bouma, GerbenBurns, Siobhan O.Forsell, Mattias N. E.Thrasher, Adrian J.Nylén, SusanneWesterberg, Lisa S.2016-11-182016Baptista, M. A. P., M. Keszei, M. Oliveira, K. K. S. Sunahara, J. Andersson, C. I. M. Dahlberg, A. J. Worth, et al. 2016. “Deletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells.” Nature Communications 7 (1): 12175. doi:10.1038/ncomms12175. http://dx.doi.org/10.1038/ncomms12175.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:29407696Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8+ T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFNγ-producing CD8+ T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8+ T cells at the expense of CD4+ T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8+ T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells.en-USJournal Article2016-11-1810.1038/ncomms12175