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Deletion of Wiskott...
Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
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Baptista, Marisa A. P. (author)
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- Keszei, Marton (author)
- Karolinska Institutet
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- Oliveira, Mariana (author)
- Karolinska Institutet
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Sunahara, Karen K. S. (author)
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- Andersson, John (author)
- Karolinska Institutet
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- Dahlberg, Carin I. M. (author)
- Karolinska Institutet
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Worth, Austen J. (author)
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- Lieden, Agne (author)
- Karolinska Institutet
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Kuo, I-Chun (author)
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Wallin, Robert P. A. (author)
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Snapper, Scott B. (author)
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- Eidsmo, Liv (author)
- Karolinska Institutet
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- Scheynius, Annika (author)
- Karolinska Institutet
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- Karlsson, Mikael C. I. (author)
- Karolinska Institutet
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Bouma, Gerben (author)
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Burns, Siobhan O. (author)
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- Forsell, Mattias N. E. (author)
- Umeå universitet,Immunologi/immunkemi
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Thrasher, Adrian J. (author)
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- Nylén, Susanne (author)
- Karolinska Institutet
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- Westerberg, Lisa S. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-07-18
- 2016
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Abstract
Subject headings
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- 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 IFN gamma-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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Baptista, Marisa ...
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Keszei, Marton
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Oliveira, Marian ...
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Sunahara, Karen ...
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Andersson, John
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Dahlberg, Carin ...
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show more...
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Worth, Austen J.
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Lieden, Agne
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Kuo, I-Chun
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Wallin, Robert P ...
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Snapper, Scott B ...
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Eidsmo, Liv
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Scheynius, Annik ...
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Karlsson, Mikael ...
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Bouma, Gerben
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Burns, Siobhan O ...
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Forsell, Mattias ...
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Thrasher, Adrian ...
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Nylén, Susanne
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Westerberg, Lisa ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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Umeå University
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Karolinska Institutet