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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Mouse β-defensin-14 for inducing the maturation of dendritic cells
Xiangwei Yuan1, Jiaxing Wang1, Mengqi Cheng1
1Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
Background:
β-defensins are an excellent antimicrobial peptide against microbial infection in which dendritic cells (DCs) play a crucial role by improving the innate and adaptive immune defense. However, it is unclear whether BDs affect DC maturation. This work aimed to study the effects of mouse β-defensin-14 (MBD-14) on DC maturation.
Methods:
Via in vitro using mouse bone marrow DCs, the maturation of DCs was evaluated by cell morphological staining, flow cytometry, endocytosis assay, and allogeneic mixed lymphocyte reaction, respectively. And it was also assessed by in vivo establishing a mouse air-pouch model for flow cytometric determination, cytokine analysis, and histological staining. Additionally, CLI-095, an inhibitor of Toll-like receptor-4 (TLR-4), was used to determine whether TLR-4 is possibly involved in DC maturation.
Results:
It was found MBD-14 promoted DCs to form more filopodia and lamellipodia, increased the expression of DC maturation markers (CD40 and MHC-II), decreased their endocytic capacity, and enhanced T-cell proliferation. The analyses of the air-pouch exudates were consistent with the in vitro results of MBD-14 activating DCs. And when CLI-095 was applied, DC maturation was inhibited partly.
Conclusions:
This work demonstrates that MBD-14 can promote the maturation of DCs in which TLR-4 is possibly involved.
Insights
Mouse beta-defensin-14 (MBD-14) promotes dendritic cell (DC) maturation, enhancing immune defense. This process involves Toll-like receptor-4 (TLR-4) and boosts T-cell responses.
Area of Science:
- Immunology
- Peptide research
- Cell biology
Background:
- Beta-defensins (BDs) are antimicrobial peptides crucial for immune defense, with dendritic cells (DCs) playing a key role.
- The impact of BDs on DC maturation remains largely uncharacterized.
- This study investigates the effect of mouse beta-defensin-14 (MBD-14) on DC maturation.
Purpose of the Study:
- To elucidate the role of MBD-14 in dendritic cell maturation.
- To investigate the underlying mechanisms, including the potential involvement of Toll-like receptor-4 (TLR-4).
Main Methods:
- In vitro studies using mouse bone marrow-derived DCs assessed maturation markers, morphology, endocytosis, and T-cell activation.
- In vivo studies utilized a mouse air-pouch model to evaluate DC activation and cytokine profiles.
- Toll-like receptor-4 (TLR-4) involvement was examined using the inhibitor CLI-095.
Main Results:
- MBD-14 enhanced DC maturation, evidenced by increased filopodia/lamellipodia formation and expression of CD40 and MHC-II.
- MBD-14 reduced DC endocytic capacity and promoted T-cell proliferation.
- In vivo results corroborated MBD-14's DC-activating effects, with partial inhibition observed upon TLR-4 blockade.
Conclusions:
- Mouse beta-defensin-14 (MBD-14) significantly promotes dendritic cell maturation.
- Toll-like receptor-4 (TLR-4) signaling is likely involved in MBD-14-induced DC maturation.
- MBD-14 enhances adaptive immune responses through DC activation.
