Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis

Rheumatology (Oxford). 2015 Sep;54(9):1596-604. doi: 10.1093/rheumatology/kev102. Epub 2015 Apr 9.

Abstract

Objective: GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA.

Methods: Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression.

Results: IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8.

Conclusion: Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.

Keywords: Th17; Th9; giant cell arteritis; small vessel vasculitis; vasa vasorum vasculitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Biopsy
  • Case-Control Studies
  • Cytokines / metabolism
  • Female
  • Giant Cell Arteritis / drug therapy
  • Giant Cell Arteritis / metabolism*
  • Giant Cell Arteritis / pathology*
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-9 / metabolism*
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Phenotype*
  • Prednisone / pharmacology
  • Prednisone / therapeutic use
  • T-Lymphocytes / pathology
  • Temporal Arteries / metabolism
  • Temporal Arteries / pathology
  • Thymic Stromal Lymphopoietin
  • Transforming Growth Factor beta / metabolism
  • Vascular System Injuries / metabolism*
  • Vascular System Injuries / pathology*

Substances

  • Biomarkers
  • Cytokines
  • Glucocorticoids
  • Interleukin-17
  • Interleukin-9
  • Transforming Growth Factor beta
  • Prednisone
  • Thymic Stromal Lymphopoietin