Leptin deficiency mitigates cutaneous inflammation in a mouse model of psoriasis

Objective To explore the effect of leptin on inflammation in psoriasis-like skin induced by imiquimod (IMQ). Methods Eight leptin gene knockout (ob/ob) obese mice and eight normal control (wt) mice were randomly divided into four groups (n=4 each), i.e. wt-IMQ, wt-vaseline, ob/ob-IMQ, ob/ob-vaseline. Mice were treated with either imiquimod (62.5 mg/back, 10 mg/ear) or Vaseline (same dose as imiquimod) for 6 consecutive days. The severity of skin lesions was evaluated with TSS score, and HE staining was used to assess inflammatory cells in the skin. Flow cytometry was used to detect the inflammatory cells in the dermis (dendritic cells, macrophages, neutrophils, etc.) and the epidermis (Langerhans cells, gdT cells), while the expression levels of IL-6, IL-17, TNF-α, IL-23 and other inflammatory factors were detected by qRT-PCR. Results ob/ob-IMQ mice displayed milder clinical symptoms, lesser increases in ear thickness, and lower TSS scores than wt-IMQ mice (all P<0.001). HE staining showed that the extent of cutaneous inflammation was lesser in ob/ob-IMQ mice than in wt-IMQ mice. The proportion of LC and gdT cells in ob/ ob-IMQ group was significantly higher than that in ob/ ob-vaseline group (t=2.78, P=0.032). The infiltration of dermal macrophages (MFs) (t=2.64, P=0.038) and neutrophils in wt-IMQ group (t=4.87, P=0.008) was more prominent than that in wt-vaseline group. However, there was no significant difference in the proportion of inflammatory cells in the epidermis and the dermis between ob/ ob-IMQ and wt-IMQ groups (both P>0.05). Expression levels of inflammatory cytokines (IL-6 and IL-17) in ob/ ob-IMQ mice were lower than that in wt-IMQ mice. Conclusions Leptin may aggravate psoriasis in individuals accompanied with obesity. Leptin deficiency counteracts IMQ-induced psoriasis-like cutaneous inflammation.