Role of p50 NF-kB in differentiation, survival and APC function

Our lab has obtained data on the role of p50 NF-kB in differentiation, survival and APC function in mice.

Tumor growth is supported by tumor stroma, which is made by matrix and infiltrating cells, such as tumor associated macrophages (TAM) and tumor associated dendritic cells (TADC). We have recently reported that TAM display massive nuclear localization of the p50 NF-kB inhibitory homodimer, which correlates with impaired inflammatory functions (Saccani et al., 2006).The functional significance of this observation was demonstrated in p50 NF-kB deficient mice, which displayed tumor growth inhibition. More recently, in order to evaluate whether this tolerogenic mechanisms may target other compartments of the immune system, we characterized the role of p50 NF-kB in dendritic cells (DC) functions, including their differentiation and maturation. Our new results demonstrate that p50 NF-kB plays a non redundant role in DC survival and APC functions. p50 NF-kB has proapoptotic functions in bone marrow derived DC, as its absence leads to a reduced rate of apoptosis/necrosis in DC activated for 48h with LPS. Moreover, after 48h of LPS stimulation, p50 -/- DC that are still alive (80% vs 40% of WT DC) display higher expression of MHC molecules and CCR7, as well as higher secretion of pro-inflammatory cytokines such as IL-1beta, TNF-alpha and IL-18. This correlates with the enhanced capability of p50-/- DC to activate T cell responses, in vitro and in vivo.
Our data suggest that targeting p50 NF-kB activity may represent a strategy to enhance selective DC functions, with potential application in anti-tumor vaccination strategies.

Protocols of antitumor vaccination will be set to explore the therapeutic potential of p50-/- DC. Both approaches aim to provide additional significant advancements in these topics.

• molecule type
• Tumor necrosis factor,
• Tumor necrosis factor alpha,
• Major histocompatibility complex,
• Interleukin-18,
• p50 subunit of NF kappaB,
• Interleukin-1 beta,
• chemokine receptor

• cell type
• T cell,
• dendritic cell,
• macrophage

• tissue type
• stroma,
• human bone marrow

• organism type
• Mus musculus

• stimulus type
• lipopolysaccharide

• experimental design type
• in vivo design experiment

• experimental factor type
• Cell line factor

created over 16 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]