Psoriasiform dermatitis after keratinocyte-restricted deletion of centrosomal protein Cep43
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Polymorphisms in the locus containing centrosomal protein 43 (Cep43) are highly associated with autoimmune diseases, including Crohn’s disease and primary biliary cholangitis, as well as cutaneous autoimmune diseases including psoriatic arthritis, oral lichen planus, and vitiligo. To address the relevance of Cep43 to cutaneous autoimmunity, we sought to define its role in the epidermis. We found that induced deletion of Cep43 in adult mouse keratinocytes <i>in vivo </i>led to a psoriasiform rash and lymphadenopathy, with robust p53 pathway activation. Cep43-deleted keratinocytes showed signs of DNA damage with micronuclei formation <i>ex vivo</i> and <i>in vivo,</i> and upregulated the DNA damage marker gH2AX. Micronuclei were recognized by cyclic GMP-AMP synthase (cGAS), linking DNA damage to the immune response. Our data are the first report of micronuclei arising in keratinocytes <i>in vivo</i> and shed light on novel mechanisms of immune activation in the skin. Christine Yokoyama<sup>1</sup>, Martin Jr. Ketcha<sup>2</sup>, Patrick Rodrigues<sup>3</sup>, Carina Dehner<sup>4</sup>, Marco Colonna<sup>3</sup> 1. Internal Medicine, Division of Dermatology, Washington University in St Louis School of Medicine, St. Louis, MO, United States. 2. Washington University in St Louis School of Medicine, St. Louis, MO, United States. 3. Pathology & Immunology, Washington University in St Louis School of Medicine, St. Louis, MO, United States. 4. Department of Pathology, Indiana University, Bloomington, IN, United States. Epidermal Structure and Barrier Function