SLURP2 Enlarges Adipocytes and Induces IL-23-Producing Macrophages in Murine Dermal Adipose Tissue

Dermal adipocytes have unique features different from visceral and subcutaneous adipocytes. Their cyclic remodelling is coupled with hair follicle (HF) cycling: expansion in the anagen and reduction in the catagen stages. Secreted Ly6/uPAR related protein 2 (SLURP2) is a non-neuronal transmitter and a ligand of both nicotinic and muscarinic acetylcholine receptors. It is upregulated in psoriatic lesions. Mouse SLURP2-deficient mice exhibit reduced adiposity and plasma cholesterol levels, in addition to palmoplantar keratoderma. However, the effects of SLURP2 on adipocytes remain unexplored. Here, we demonstrated that SLURP2 regulates murine dermal adipocyte size independently of HF cycling and upregulates interleukin (IL)-23 gene expression following intradermal injection of recombinant human SLURP2-Fc protein (rSLURP2) and phosphate-buffered saline (control) at different dorsal sites of C57BL/6J mice after depilation. SLURP2 enlarged dermal adipocytes independently of HF cycles by inhibiting sterol regulatory element-binding protein-1, a transcription factor involved in cholesterol and fatty acid synthesis, which leads to the activation of cholesterol synthesis followed by expansion of the plasma and lipid droplet membrane. Immunohistochemical staining of paired mirror sections revealed a statistically significant increase in the ratio of IL-23-producing macrophages in the dermal adipose tissue of rSLURP2-injected skin compared with the control. Furthermore, IL-23p19 gene expression was significantly upregulated in rSLURP2-treated skin. Taken together with the previous findings, the present study showed that SLURP2 has inflammatory and metabolic effects. Dermal adipose tissues may serve as a source of IL-23 in psoriatic lesions.