Immunolocalization and Expression of JAK/STAT Signaling Molecules in the Skin of NCSTN Knockout Mouse

Mutations in the NCSTN gene are believed to be involved in the pathogenesis of acne inversa (AI). Further, certain cytokines are overexpressed in the inflammatory milieu of AI skin. Considering its central role in cytokine regulation, the JAK/STAT signaling pathway should be examined as a pathogenic factor and potential therapeutic target in AI.

NCSTNflox/+, CAGGCre-ERTM mice were given 10 mg/kg/day tamoxifen for 6 days. Knockout of the NCSTN gene was confirmed by PCR. The levels of JAK1, JAK2, JAK3, and TYK2 in the skin tissue of NCSTN conditional knockout mice and WT mice were measured by IHC.

By objective scoring using ImageJ software, JAK2 (p = 0.013) expression was increased in the dermis of KO mice, and JAK1 (p = 0.032), JAK3 (p = 0.028), and TYK2 (p = 0.029) were upregulated in the epidermis of KO mice versus WT mice.

This study suggests that the JAK/STAT pathway is important in AI, rendering it a potential therapeutic target. Targeting the JAK1/2 may be more prominent in the treatment of HS.