The LCE3D/TGF-β1 Axis in atopic dermatitis: Expression profiling, clinical significance, and mechanistic insights into epithelial-immune crosstalk.

BACKGROUND

AD involves barrier dysfunction and immune imbalance. Roles of LCE3D and TGF-β1 remain unclear.

METHODS

Bioinformatics analysis (GEO: GSE130588), RT-qPCR, ELISA, and Western blot were performed in 30 CE patients and 30 controls, including 15 serum pairs. TNF-α-stimulated HaCaT and NHEK cells were used to establish an AD-like model. LCE3D knockdown and overexpression were conducted, and TGF-β1 silencing was used to explore mechanistic interaction.

RESULTS

LCE3D was upregulated in AD tissues and serum, negatively correlated with TGF-β1, and associated with disease severity and IL-4/IFN-γ imbalance. In vitro, TNF-α increased LCE3D and IL-4 while decreasing IFN-γ and TGF-β1. LCE3D knockdown increased TGF-β1, IFN-γ, and barrier proteins (involucrin, loricrin) and reduced IL-4, whereas overexpression showed opposite effects. TGF-β1 silencing reversed these effects.

CONCLUSIONS

LCE3D promotes AD progression by suppressing TGF-β1, driving Th2/Th1 imbalance and epidermal barrier dysfunction. The LCE3D/TGF-β1 axis is a potential therapeutic target.