The E3 ligase c-Cbl regulates dendritic cell activation |
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Authors: | Chiou Shin-Heng Shahi Payam Wagner Ryan T Hu Hongbo Lapteva Natalia Seethammagari Mamatha Sun Shao-Cong Levitt Jonathan M Spencer David M |
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Affiliation: | Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA. |
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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)-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. |
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Keywords: | c‐Cbl dendritic cell E3 ubiquitin ligase p105 IL12p70 |
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