Leptin deficiency in mice counteracts imiquimod (IMQ)‐induced psoriasis‐like skin inflammation while leptin stimulation induces inflammation in human keratinocytes

Abstract

Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis.

Metabolic syndrome and risk of incident psoriasis: prospective data from the HUNT Study, Norway

“…Many cytokines are also found to be common in both psoriasis pathogenesis and lipoprotein dysregulation . In addition, adipose tissue produces adipokines, which are drivers of chronic inflammation . Furthermore, one study found shared genes between psoriasis and dyslipidaemia, hypertension and increased coronary artery disease, while others have found no genetic association between psoriasis and metabolic syndrome or coronary artery disease …”

Obesity and inflammatory skin diseases

“…In psoriasis patients, leptin levels showed correlation with psoriasis seve rity [36] . Furthermore, leptin-deficient (ob/ob) mice exhibit impaired IL-17A and IL-22 mRNA expression as well as reduced epidermal hyperplasia in an imiquimod (IMQ)-induced psoriasis model [37] . In vitro, leptin induces proliferation and production of several pro-inflammatory proteins on human keratinocytes [37] .…”

“…Furthermore, leptin-deficient (ob/ob) mice exhibit impaired IL-17A and IL-22 mRNA expression as well as reduced epidermal hyperplasia in an imiquimod (IMQ)-induced psoriasis model [37] . In vitro, leptin induces proliferation and production of several pro-inflammatory proteins on human keratinocytes [37] . These results suggest that leptin may exacerbate the condition in psoriasis.…”

Psoriasis – What′s Up ?

“…Adipocytes are the primary source of leptin, an adipokine with far‐reaching effects connecting the neuroendocrine and immune systems . In the current issue, Stjernholm et al . make use of the imiquimod mouse model to investigate the link between leptin and psoriasis.…”

“…[14][15][16][17] Adipocytes are the primary source of leptin, an adipokine with far-reaching effects connecting the neuroendocrine and immune systems. [18] In the current issue, Stjernholm et al [19] make use of the imiquimod mouse model to investigate the link between leptin and psoriasis. The imiquimod model has also been used by Cho et al [20] to address the (indirect) interaction of poly(I:C) with PD-L1.…”