Deletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells

Marisa A. P. Baptista, Marton Keszei, Mariana Oliveira, Karen K. S. Sunahara, John Andersson, Carin I. M. Dahlberg, Austen J. Worth, Agne Liedén, I-Chun Kuo, Robert P. A. Wallin, Scott B. Snapper, Liv Eidsmo, Annika Scheynius, Mikael C. I. Karlsson, Gerben Bouma, Siobhan O. Burns, Mattias N. E. Forsell, Adrian J. Thrasher, Susanne Nylén and Lisa S. Westerberg ()
Additional contact information
Marisa A. P. Baptista: Karolinska Institutet
Marton Keszei: Karolinska Institutet
Mariana Oliveira: Karolinska Institutet
Karen K. S. Sunahara: Karolinska Institutet
John Andersson: Translational Immunology Unit, Karolinska Institutet and Karolinska University Hospital
Carin I. M. Dahlberg: Karolinska Institutet
Austen J. Worth: University College London Institute of Child Health
Agne Liedén: Karolinska Institutet
I-Chun Kuo: Yong Loo Lin School of Medicine, National University of Singapore
Robert P. A. Wallin: Karolinska Institutet
Scott B. Snapper: Children's Hospital, Harvard Medical School
Liv Eidsmo: Dermatology and Venereology Unit, Karolinska Institutet
Annika Scheynius: Translational Immunology Unit, Karolinska Institutet and Karolinska University Hospital
Mikael C. I. Karlsson: Karolinska Institutet
Gerben Bouma: University College London Institute of Child Health
Siobhan O. Burns: University College London Institute of Child Health
Mattias N. E. Forsell: Karolinska Institutet
Adrian J. Thrasher: University College London Institute of Child Health
Susanne Nylén: Karolinska Institutet
Lisa S. Westerberg: Karolinska Institutet

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract Wiskott–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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12175

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DOI: 10.1038/ncomms12175

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