SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases

Abstract

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4⁺ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Keywords: NF-κB; Psoriasis; Rosacea; SERPINB3/B4; Skin inflammation.