Molecular profiling and gene expression analysis in cutaneous sarcoidosis: the role of interleukin-12, interleukin-23, and the T-helper 17 pathway

J Am Acad Dermatol. 2012 Jun;66(6):901-10, 910.e1-2. doi: 10.1016/j.jaad.2011.06.017. Epub 2011 Sep 15.


Background: Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue.

Objective: We sought to explore the role of the T-helper (Th)1 and Th17 pathways in sarcoidosis.

Methods: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood.

Results: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (≥2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway.

Limitations: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally.

Conclusion: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis.

Publication types

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

MeSH terms

  • Adult
  • Female
  • Gene Expression Profiling*
  • Humans
  • Interleukin-12 / physiology*
  • Male
  • Microarray Analysis
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • STAT3 Transcription Factor / physiology
  • Sarcoidosis / immunology
  • Sarcoidosis / physiopathology*
  • Signal Transduction / physiology*
  • Skin Diseases / physiopathology*
  • Th1 Cells / physiology*
  • Th17 Cells / physiology*
  • Up-Regulation / physiology


  • STAT3 Transcription Factor
  • Interleukin-12