The E3 ligase c-Cbl regulates dendritic cell activation.


Publication Type:

Source:

EMBO Rep, Volume 12, Issue 9, p.971-9 (2011)

Keywords:

Animals, Antigens, Nuclear, Chromosomal Proteins, Non-Histone, Dendritic Cells, Female, Interleukin-12, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B p50 Subunit, Proto-Oncogene Proteins c-cbl, Signal Transduction, Toll-Like Receptors

Abstract:

<p>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.</p>