Ion metabolizers mediate inflammation in pustular skin disorders

Published Online: November 21, 2016

Pustular skin disorders are a category of difficult-to-treat and potentially life-threatening conditions. Their common symptoms include the appearance of pustules, circumscribed collections of neutrophils in the skin. The molecular basis of most pustular skin conditions has remained unknown.

In a study recently published in The Journal of Allergy and Clinical Immunology (JACI), Liang and colleagues describe an investigation of the molecular mechanism underlying three pustular skin disorders: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), and acute generalized exanthematous pustulosis (AGEP).

Through genome-wide gene expression profiling of skin biopsy specimens obtained from patients with GPP, PP and AGEP, molecules and pathways related to neutrophil chemotaxis were identified as common alterations, which is consistent with the pustular phenotypes. Expression of two 6-transmembrane epithelial antigens of the prostate (STEAP) proteins, STEAP1 and STEAP4, which were originally identified to mediate ion metabolism, was increased in patient’s skin. STEAP1 and STEAP4 were co-expressed with inflammatory proteins including IL-1, IL-36, CXCL1 and CXCL8. Reduction in STEAP1/4 levels impaired induction of a broad spectrum of pro-inflammatory cytokines and neutrophil chemotaxins, as well as the ability of keratinocytes to induce neutrophil chemotaxis.

The authors concluded that transcriptomic changes in the three pustular skin disorders converged on neutrophil chemotaxis and neutrophil-driven inflammatory processes. STEAP1 and STEAP4 promote the induction of pro-inflammatory, neutrophil-activating cytokines. These findings open up possibilities in targeting the STEAP pathways for the treatment of pustular skin conditions and other disorders that share similar inflammatory profiles.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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