Lipocalin‐2 exacerbates psoriasiform skin inflammation by augmenting T‐helper 17 response

Lipocalin‐2 ( LCN 2) is an antimicrobial protein and adipokine associated with insulin resistance, obesity and atherosclerotic disease. Psoriasis is a T‐helper (Th)1/Th17‐mediated, chronic inflammatory dermatosis related to metabolic syndromes and serum LCN 2 levels are elevated in psoriatic patients. We examined the in vivo effects of LCN 2 on topical imiquimod ( IMQ )‐induced psoriasiform skin in BALB /c mice and in vitro on human keratinocytes ( KC ). Clinically, i.p. injected LCN 2 exacerbated erythema and scaling in IMQ ‐treated murine skin compared with phosphate‐buffered saline injection alone, and it augmented interleukin ( IL) ‐17A, IL ‐17F, IL ‐22, IL ‐23p19, IL ‐12p40, CCL 20, tumor necrosis factor‐α, chemokine ( C‐X‐C motif) ligand ( CXCL )1, CXCL 2, DEFB 4, DEFB 14, LCN 2 and S100A7 mRNA levels of IMQ ‐treated murine skin while it did not increase the mRNA levels of interferon‐γ, IL ‐12p35 or CXCL 10. LCN 2 in synergy with IL ‐17 increased mRNA levels of CCL 20, LCN 2 and DEFB 4A but not of CXCL 10 in human KC in vitro . These results suggest that LCN 2 enhances the expression of Th17 cytokines/chemokines and antimicrobial peptides in murine IMQ ‐treated psoriatic skin and KC . LCN 2 may potentiate the development of psoriasis via the enhancement of Th17‐ and antimicrobial peptide‐mediated inflammation.