SERPINB3/B4 Is Increased in Psoriasis and Rosacea Lesions and Has Proinflammatory Effects in Mouse Models of these Diseases

Wenqin Xiao; Ke Sha; Mei Wang; Zixin Tan; Yunying Wang; San Xu; Zhixiang Zhao; Qian Wang; Hongfu Xie; Mengting Chen; Zhili Deng; Ji Li

doi:10.1016/j.jid.2024.04.011

SERPINB3/B4 Is Increased in Psoriasis and Rosacea Lesions and Has Proinflammatory Effects in Mouse Models of these Diseases

J Invest Dermatol. 2024 May 10:S0022-202X(24)00367-1. doi: 10.1016/j.jid.2024.04.011. Online ahead of print.

Authors

Wenqin Xiao¹, Ke Sha², Mei Wang¹, Zixin Tan¹, Yunying Wang¹, San Xu¹, Zhixiang Zhao¹, Qian Wang³, Hongfu Xie¹, Mengting Chen¹, Zhili Deng⁴, Ji Li⁵

Affiliations

¹ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
² Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
³ Hunan Binsis Biotechnology, Changsha, China.
⁴ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: dengzhili@csu.edu.cn.
⁵ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. Electronic address: liji_xy@csu.edu.cn.

PMID: 38735363
DOI: 10.1016/j.jid.2024.04.011

Abstract

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these 2 conditions are poorly understood. In this study, we reveal that both patients with psoriasis and those with rosacea as well as their mouse 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 2 diseases.

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