Details

Autor(en) / Beteiligte

• Baptista, Marisa A P
• Keszei, Marton
• Oliveira, Mariana
• Sunahara, Karen K S
• Andersson, John
• Dahlberg, Carin I M
• Worth, Austen J
• Liedén, Agne
• Kuo, I-Chun
• Wallin, Robert P A
• Snapper, Scott B
• Eidsmo, Liv
• Scheynius, Annika
• Karlsson, Mikael C I
• Bouma, Gerben
• Burns, Siobhan O
• Forsell, Mattias N E
• Thrasher, Adrian J
• Nylén, Susanne
• Westerberg, Lisa S

Titel

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

Ist Teil von

• Nature communications, 2016-07, Vol.7 (1), p.12175-15, Article 12175

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.