TY  - JOUR
A1  - Kuznetsov, Nikolai V.
A1  - Almuzzaini, Bader
A1  - Kritikou, Joanna S.
A1  - Baptista, Marisa A. P.
A1  - Oliveira, Mariana M. S.
A1  - Keszei, Marton
A1  - Snapper, Scott B.
A1  - Percipalle, Piergiorgio
A1  - Westerberg, Lisa S.
T1  - Nuclear Wiskott-Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells
JF  - Genome Medicine
N2  - Background
The Wiskott–Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined.

Methods
We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4\(^+\) T cells.

Results
WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4\(^+\) T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF)12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASp\(^{L272P}\) and WASp\(^{I296T}\) had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus.

Conclusions
These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.
KW  - Medicine
KW  - WASp
KW  - T cells
KW  - ChIP-seq
KW  - Wiskott-Aldrich syndrome
KW  - TCF1
KW  - TCF12
KW  - Nucleus
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173486
VL  - 9
ER  - 
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  -