A novel pro-angiogenic function for interferon-γ-secreting natural killer cells

Area of Science:

• Immunology
• Ophthalmology
• Angiogenesis research

Background:

• Inflammatory angiogenesis is crucial for various ocular diseases.
• The role of natural killer (NK) cells in this process remains largely unexplored.

Purpose of the Study:

• To investigate the function of NK cells in inflammatory angiogenesis using mouse models.
• To determine the impact of NK cell depletion on ocular angiogenic responses.

Main Methods:

• Utilized cornea BFGF micropellet and laser-induced choroidal neovascularization (CNV) mouse models.
• Depleted NK cells using anti-NK1.1 antibody and assessed angiogenesis via immunohistochemistry.
• Quantified vascular endothelial growth factors (VEGF), IFN-γ, and TNF-α levels using qPCR and flow cytometry.
• Performed in vitro coculture assays with macrophages, NK cells, and endothelial cells.

Main Results:

• NK cell depletion significantly reduced corneal angiogenesis and CNV.
• Reduced macrophage infiltration and VEGF expression (VEGF-A, VEGF-C, VEGFR3) were observed in NK cell-depleted corneas.
• NK cell depletion decreased CNV areas and VEGF/IFN-γ expression in the choroid.
• In vitro, NK cells enhanced endothelial cell proliferation via an IFN-γ-dependent increase in VEGF.

Conclusions:

• NK cells possess a novel pro-angiogenic function.
• IFN-γ-secreting NK cells induce angiogenesis by upregulating macrophage VEGF production.