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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Effect of Cytomegalovirus Recombinant Phosphoprotein 150 (pp150) on Maturation and Function of Murine Dendritic
Yousef Nikmanesh1, Shohreh Shahmahmoodi, Ramin Yaghobi
1Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Background:
Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated.
Objective:
To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs).
Methods:
Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized. Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs.
Results:
A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α.
Conclusion:
Despite improvements in maturity status, pp150-stimulated DCs did not seem to be able to induce Th1 or Th2 immunity. In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's mechanism of action. However, it is necessary to conduct further investigations to corroborate these observations.
Insights
Human cytomegalovirus (HCMV) tegument protein pp150 enhances dendritic cell (DC) maturity but promotes Th17 immunity, not Th1 or Th2 responses. This suggests pp150
Area of Science:
- Immunology
- Virology
Background:
- Tegument protein pp150 is crucial for cytomegaloviruses (CMVs) and a potential target for human cytomegalovirus (HCMV) treatment.
- The precise role of pp150 in immune regulation remains unclear.
Purpose of the Study:
- To investigate the impact of pp150 on the maturation and function of murine dendritic cells (DCs).
Main Methods:
- Assessed DC maturity (CD40, CD86, MHC-II expression) and phagocytic capacity.
- Analyzed gene expression (ROR-γ, GATA-3, T-bet, FOXP-3) and protein expression (cytokines like INF-γ, IL-4, IL-17A, IL-22) in co-cultured T cells.
Main Results:
- pp150 stimulation increased DC expression of CD40, CD86, and CCR7, while reducing phagocytosis.
- T cells co-cultured with pp150-stimulated DCs showed elevated ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α.
Conclusions:
- pp150-stimulated DCs exhibit enhanced maturity but do not induce Th1 or Th2 immunity.
- Th17-related cytokines (IL-17A, IL-22) appear to be key inflammatory mediators in pp150-stimulated DCs.
- Further research is needed to confirm these findings regarding pp150's immunomodulatory effects.

