Evidence that a neutrophil-keratinocyte crosstalk is an early target of IL-17A inhibition in psoriasis

Exp Dermatol. 2015 Jul;24(7):529-35. doi: 10.1111/exd.12710. Epub 2015 May 8.


The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. We examined the clinical and immunological response patterns of 100 subjects with moderate-to-severe psoriasis receiving 3 different intravenous dosing regimens of the anti-IL-17A antibody secukinumab (1 × 3 mg/kg or 1 × 10 mg/kg on Day 1, or 3 × 10 mg/kg on Days 1, 15 and 29) or placebo in a phase 2 trial. Baseline biopsies revealed typical features of active psoriasis, including epidermal accumulation of neutrophils and formation of microabscesses in >60% of cases. Neutrophils were the numerically largest fraction of infiltrating cells containing IL-17 and may store the cytokine preformed, as IL-17A mRNA was not detectable in neutrophils isolated from active plaques. Significant clinical responses to secukinumab were observed 2 weeks after a single infusion, associated with extensive clearance of cutaneous neutrophils parallel to the normalization of keratinocyte abnormalities and reduction of IL-17-inducible neutrophil chemoattractants (e.g. CXCL1, CXCL8); effects on numbers of T cells and CD11c-positive dendritic cells were more delayed. Histological and immunological improvements were generally dose dependent and not observed in the placebo group. In the lowest-dose group, a recurrence of neutrophils was seen in some subjects at Week 12; these subjects relapsed faster than those without microabscesses. Our findings are indicative of a neutrophil-keratinocyte axis in psoriasis that may involve neutrophil-derived IL-17 and is an early target of IL-17A-directed therapies such as secukinumab.

Keywords: IL-17A; neutrophils; psoriasis; secukinumab.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Cell Communication / immunology
  • Dose-Response Relationship, Immunologic
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Keratinocytes / immunology*
  • Keratinocytes / pathology
  • Middle Aged
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Psoriasis / therapy*
  • Time Factors
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • IL17A protein, human
  • Interleukin-17
  • secukinumab