TY  - JOUR
A1  - Baptista, Marisa A.P.
A1  - Keszei, Marton
A1  - Oliveira, Mariana
A1  - Sunahara, Karen K.S.
A1  - Andersson, John
A1  - Dahlberg, Carin I.M.
A1  - Worth, Austen J.
A1  - Liedén, Agne
A1  - Kuo, I-Chun
A1  - Wallin, Robert P.A.
A1  - Snapper, Scott B.
A1  - Eidsmo, Liv
A1  - Scheynius, Annika
A1  - Karlsson, Mikael C.I.
A1  - Bouma, Gerben
A1  - Burns, Siobhan O.
A1  - Forsell, Mattias N.E.
A1  - Thrasher, Adrian J.
A1  - Nylén, Susanne
A1  - Westerberg, Lisa S.
T1  - Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
JF  - Nature Communications
N2  - Wiskott–Aldrich syndrome (WAS) is caused by loss-of-function mutations in theWASp 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 CD8þ T cells. Using two different skin
pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin
and increased expansion of IFNg-producing CD8þ T cells in the draining lymph node and
spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8þ
T cells at the expense of CD4þ T cells. WASp-deficient dendritic cells induce increased
cross-presentation to CD8þ 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.
KW  - Cell signalling
KW  - Dendritic cells
KW  - Disease genetics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165966
VL  - 7
ER  -