Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa

J Invest Dermatol. 2016 Sep;136(9):1768-1780. doi: 10.1016/j.jid.2016.04.036. Epub 2016 May 17.

Abstract

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating, follicular disease of the skin. Despite a high prevalence in the general population, the physiopathology of HS remains poorly understood. The use of antibiotics and immunosuppressive agents for therapy suggests a deregulated immune response to microflora. Using cellular and gene expression analyses, we found an increased number of infiltrating CD4(+) T cells secreting IL-17 and IFN-γ in perilesional and lesional skin of patients with HS. By contrast, IL-22-secreting CD4(+) T cells are not enriched in HS lesions contrasting with increased number of those cells in the blood of patients with HS. We showed that keratinocytes isolated from hair follicles of patients with HS secreted significantly more IL-1β, IP-10, and chemokine (C-C motif) ligand 5 (RANTES) either constitutively or on pattern recognition receptor stimulations. In addition, they displayed a distinct pattern of antimicrobial peptide production. These findings point out a functional defect of keratinocytes in HS leading to a balance prone to inflammatory responses. This is likely to favor a permissive environment for bacterial infections and chronic inflammation characterizing clinical outcomes in patients with HS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Disease Progression
  • Female
  • Flow Cytometry
  • Hidradenitis Suppurativa / blood*
  • Hidradenitis Suppurativa / physiopathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Microarray Analysis / methods
  • RNA / metabolism
  • Risk Assessment
  • Sampling Studies
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Cytokines
  • RNA