The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis

Hum Immunol. 2015 Jan;76(1):22-9. doi: 10.1016/j.humimm.2014.12.008. Epub 2014 Dec 11.

Abstract

Objective: The objective was to survey the expression and localization of Th17-related cytokines and their correlation with skin lesion severity in early systemic sclerosis (SSc).

Methods: The mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) from 21 SSc patients and 12 healthy controls (HC). The protein expression was examined by immunohistochemistry (IHC) and Western blotting.

Results: The RT-qPCR analysis showed a significantly higher expression of IL-17A, IL-21, IL-22, IL-26, IL-17RA, IL-21R, and IL-22R1 mRNA; consistently, the IHC analysis showed an over-expression of IL-17RA, IL-21R and IL-22R1 and the Western blotting analysis showed an over-expression of IL-17A, IL-21, IL-21R and IL-22R1 in early SSc skin lesions. The mRNA levels of IL-21 were higher in diffuse cutaneous than limited cutaneous SSc lesions. The mRNA expression of IL-26, IL-22, IL-22R1, mRNA and protein expression of IL-17A, IL-21, IL-21R were positively correlated with the modified Rodnan skin score of SSc. In addition, the mRNA levels of ICAM-1 were positively correlated with IL-17A/IL-17RA, and VEGFA and IL-4 were both positively correlated with IL-21/IL-21R, while TGF-β were moderately negatively correlated with IL-22/IL-22R1.

Conclusions: Th17 cytokines contribute to progression in early SSc skin lesions. IL-21/IL-21R could act as potential biomarkers presenting early SSc skin lesions severity.

Keywords: Skin lesion; Systemic sclerosis; Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Early Diagnosis
  • Female
  • Gene Expression
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-21 Receptor alpha Subunit / genetics
  • Interleukin-21 Receptor alpha Subunit / immunology*
  • Interleukin-22
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukins / genetics
  • Interleukins / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / immunology
  • Scleroderma, Systemic / diagnosis*
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / metabolism
  • Severity of Illness Index
  • Skin / immunology
  • Skin / metabolism*
  • Skin / pathology
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology

Substances

  • ICAM1 protein, human
  • IL17A protein, human
  • IL17RA protein, human
  • IL21R protein, human
  • IL26 protein, human
  • IL4 protein, human
  • Interleukin-17
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Transforming Growth Factor beta
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • interleukin-22 receptor
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • interleukin-21