P102 Importance of the inflammation in adipose tissue as exacerbating factor of obesity-associated psoriasis

Abstract Obesity is a risk factor for psoriasis. However, it is not necessarily detrimental when excess fat is stored in healthy adipose tissue. To identify pathogenic association between obesity and psoriasis, we investigated an obese mouse model of psoriasis induced by topical imiquimod or dermal interleukin (IL)-23 injection. Obese mice exhibited aggravated psoriatic dermatitis with pronounced systemic inflammatory responses when exposed to imiquimod. Notably, imiquimod-induced psoriatic dermatitis in obese mice significantly reduced fat mass. Further, pronounced monocyte–macrophage infiltration of perigonadal adipose tissue, increased expression of genes linked to inflammation, and upregulation of cell death-associated molecules were evident in obese mice treated with imiquimod compared with their lean counterparts. In contrast, IL-23 injection could induce similar features of psoriatic inflammation in obese and lean mice, without causing adipose tissue destruction or a systemic increase in inflammatory mediators. Obese adipose tissue of mice with imiquimod-induced psoriatic inflammation featured genetic and epigenetic changes in adipocytes and shifts in macrophage compartments towards disturbed homeostasis using multiomic single-nucleus sequencing targeting RNA and accessible chromatin. Our study demonstrates that disrupted homeostasis in obese adipose tissue amplifies the systemic manifestations of psoriasis, highlighting the potential for developing interventions to control obesity-associated exacerbation of psoriasis.