Recombinant ferritin nanoparticles can induce dendritic cell maturation through TLR4/NF-κB pathway

Area of Science:

• Immunology
• Nanotechnology
• Biochemistry

Background:

• Dendritic cells (DCs) are crucial for initiating and regulating immune responses.
• The mechanism by which ferritin induces DC maturation is not well understood.

Purpose of the Study:

• To investigate how recombinant ferritin nanoparticles (RFNps) induce dendritic cell (DC) maturation.
• To explore the potential of RFNps as carriers in DC-based vaccines.

Main Methods:

• Recombinant ferritin nanoparticles (RFNps) were prepared using a baculovirus expression vector system.
• Bone marrow-derived DCs (BMDCs) were treated with RFNps, and their maturation was assessed via surface molecule expression, cytokine production, and antigen capture capacity.
• NF-κB signaling pathway activation was analyzed through IκBα and NF-κB (p65) phosphorylation and translocation.
• The role of TLR4 and NF-κB was confirmed using specific inhibitors.
• T-cell proliferation and differentiation were evaluated after co-culture with RFNp-treated BMDCs.

Main Results:

• RFNps formed spherical, hollow cage-like structures approximately 12 nm in diameter.
• RFNps induced BMDC maturation, evidenced by increased MHC II, CD80, CD86, and CD40 expression.
• Pro-inflammatory cytokine production (IL-6, IL-12, TNF-α, IFN-γ) increased, while antigen capture capacity decreased.
• RFNps activated the NF-κB pathway, promoting IκBα and NF-κB (p65) phosphorylation and nuclear translocation.
• Inhibition of TLR4 or NF-κB suppressed RFNp-induced DC maturation markers and signaling.
• RFNp-treated BMDCs enhanced T-cell proliferation and Th1/Th2 differentiation.

Conclusions:

• RFNps effectively induce dendritic cell maturation through TLR4 and NF-κB signaling.
• The ability of RFNps to mature DCs and promote T-cell responses highlights their potential as vaccine carriers.