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The E3 ligase c-Cbl regulates dendritic cell activation.

ABSTRACT: 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)-?B activity. In addition, c-Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF-?B. 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.

SUBMITTER: Chiou SH

PROVIDER: S-EPMC3166462 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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The E3 ligase c-Cbl regulates dendritic cell activation.

Chiou Shin-Heng SH Shahi Payam P Wagner Ryan T RT Hu Hongbo H Lapteva Natalia N Seethammagari Mamatha M Sun Shao-Cong SC Levitt Jonathan M JM Spencer David M DM

EMBO reports 20110901 9

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 establishe ...[more]

PMID: 21799517

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