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The E3 ligase c‐Cbl regulates dendritic cell activation
Author(s) -
Chiou ShinHeng,
Shahi Payam,
Wagner Ryan T,
Hu Hongbo,
Lapteva Natalia,
Seethammagari Mamatha,
Sun ShaoCong,
Levitt Jonathan M,
Spencer David M
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.143
Subject(s) - microbiology and biotechnology , proinflammatory cytokine , ubiquitin ligase , dendritic cell , acquired immune system , biology , t cell , toll like receptor , innate immune system , chemistry , immune system , immunology , ubiquitin , inflammation , biochemistry , gene
The activation of innate and adaptive immunity is always balanced by inhibitory signalling mechanisms to maintain tissue integrity. We have identified the E3 ligase c‐Cbl––known for its roles in regulating lymphocyte signalling––as a modulator of dendritic cell activation. In c‐Cbl‐deficient dendritic cells, Toll‐like receptor‐induced expression of proinflammatory factors, such as interleukin‐12, is increased, correlating with a greater potency of dendritic‐cell‐based vaccines against established tumours. This proinflammatory phenotype is accompanied by an increase in nuclear factor (NF)‐κB activity. In addition, c‐Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF‐κB. Our data indicate that c‐Cbl has a crucial, RING‐domain‐dependent role in regulating dendritic cell maturation, probably by facilitating the regulatory function of p105 and/or p50.