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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Promoting effect of polysaccharide isolated from Mori fructus on dendritic cell maturation
Bo Ram Shin1, Hyung Sook Kim, Mi Jung Yun
1College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
Abstract:
Maturation of dendritic cells (DCs) is usually attenuated in the tumor microenvironment, which is an important immunological problem in DC-based immunotherapy of cancer. In this study, we report the effect of a Mori fructus polysaccharide (MFP) on DC maturation. MFP was treated to DCs generated from mouse BM cells. MFP induced phenotypic maturation of DCs, as proven by the increased expression of CD40, CD80/86, and MHC-I/II molecules. MFP induced functional maturation of DCs, in that MFP increased the expression of IL-12, IL-1β, TNF-α, and IFN-β, decreased antigen capture capacity, and enhanced allogenic T cell stimulation. MFP efficiently induced maturation of DCs from C3H/HeN mice having normal toll-like receptor4 (TLR4), but not DCs from C3H/HeJ mice having mutated TLR4, suggesting that TLR4 might be one of the membrane receptors of MFP. As a mechanism of action, MFP increased phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear translocation of NF-κB p65 subunit, which were important signal molecules downstream from TLR4. These data suggest that MFP induces DC maturation through TLR4 and MFP can be used as an adjuvant in DC-based cancer immunotherapy.
Insights
A Mori fructus polysaccharide (MFP) promotes dendritic cell (DC) maturation by activating toll-like receptor 4 (TLR4). This suggests MFP could be a valuable adjuvant for DC-based cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Dendritic cell (DC) maturation is crucial for effective cancer immunotherapy but is often impaired within the tumor microenvironment.
- Developing strategies to enhance DC maturation is essential for improving anti-cancer immune responses.
Purpose of the Study:
- To investigate the effects of Mori fructus polysaccharide (MFP) on the maturation of dendritic cells (DCs).
- To elucidate the underlying mechanisms of MFP-induced DC maturation and its potential as an adjuvant in cancer immunotherapy.
Main Methods:
- Dendritic cells were generated from mouse bone marrow (BM) cells and treated with MFP.
- DC maturation was assessed by analyzing phenotypic markers (CD40, CD80/86, MHC-I/II) and functional parameters (cytokine production, antigen capture, T cell stimulation).
- The role of toll-like receptor 4 (TLR4) and downstream signaling pathways (MAPK, NF-κB) was investigated.
Main Results:
- MFP treatment significantly enhanced phenotypic maturation of DCs, evidenced by increased expression of CD40, CD80/86, and MHC-I/II molecules.
- MFP induced functional maturation, increasing pro-inflammatory cytokine secretion (IL-12, IL-1β, TNF-α, IFN-β), reducing antigen capture, and boosting allogeneic T cell stimulation.
- MFP-mediated DC maturation was dependent on functional TLR4, involving the activation of MAPK and NF-κB signaling pathways.
Conclusions:
- MFP effectively induces both phenotypic and functional maturation of dendritic cells.
- The mechanism involves TLR4 activation, leading to downstream signaling events.
- MFP shows promise as an adjuvant for enhancing DC-based cancer immunotherapy.

