Dual roles of dermal adipogenesis in initiating and resolving neutrophilic skin inflammation

Dermal white adipose tissue (dWAT) is highly plastic and pivotal in host defense; however, its role in controlling neutrophil function remains unstudied. Here we found that Imiquimod-induced psoriatic skin inflammation prompted a dermal adipogenesis response, with preadipocyte expansion followed by differentiation into adipocytes. By single-cell RNAseq of the imiquimod skin samples, we found that dWAT was the primary site for initial neutrophil influx and activation, facilitated by interactions between neutrophils and preadipocytes via the IL1β-IL1R and CXCL1-CXCR2 pathways. IL1β-activated preadipocytes secreted CXCL1 and SAA3 to boost neutrophilic inflammation. Prolonged inflammation in preadipocytes led to their differentiation into early adipocytes, secreting anti-inflammatory lipids to resolve neutrophilic inflammation and restore homeostasis. Psoriasis-like skin inflammation was induced on mouse skin by daily topical application of imiquimod (IMQ) for 5 days. Dorsal skin biopsies were collected from 2 groups, including control and IMQ-treated adult mice (C57BL/6, 2 month, female). Skin samples were subjected to enzymatic digestion and dead cell removal procedures to isolate single viable cells for single-cell cDNA library prep and RNA-sequencing using the 10X Genomics Chromium system and Illumina Novaseq6000 platform.