The IL-36γ/PEDF/PPARγ signalling pathway plays an anti-inflammatory role in Candida albicans keratitis.

Fungal keratitis caused by Candida albicans (CA) is a common, disabling eye disease with a complex immune response system, affecting diagnosis, treatment, and prognosis. The specific regulatory roles and interactions of IL-36γ and pigment epithelium-derived factor (PEDF) in this disease remain largely unclarified. Additionally, the influence of miR-204-5p on the expression and anti-inflammatory functions of IL-36γ and PEDF in CA keratitis is insufficiently explored. Therefore, research focused on understanding the disease's pathogenesis and immune regulation. Human corneal epithelial cells treated with heat-killed CA showed anti-inflammatory responses from IL36γ and PEDF, confirmed via western blot, PCR, and ELISA. Transfection of small interfering RNA and recombinant protein granules showed PEDF exerts immunoprotected regulatory mechanisms by inhibiting NF-κB via PPARγ. Analysis of multiple miRNA target gene prediction databases and literature revealed that miR-204-5p is differentially expressed in fungal keratitis. PCR and dual luciferase reporter assays confirmed that miR-204-5p directly binds to PEDF mRNA, negatively regulating IL36γ and PEDF expression. Consequently, both PEDF and IL-36 γ exhibit anti-inflammatory effects in CA keratitis. PEDF may inhibit the NF-κB signaling pathway through the PPAR γ pathway. In addition, miR-204-5p inhibits the mRNA expression of IL-36 γ and PEDF, exacerbating inflammation. This provides a theoretical basis for new methods and drug targets for the prevention and treatment of CA keratitis, and promotes the clinical application of IL-36 γ/PEDF.