Interleukin-36α axis is modulated in patients with primary Sjögren's syndrome

Clin Exp Immunol. 2015 Aug;181(2):230-8. doi: 10.1111/cei.12644. Epub 2015 Jun 3.


The aim of this study was to investigate the expression of the interleukin (IL)-36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 non-Sjögren's syndrome patients (nSS) patients. Serum IL-36α was assayed by enzyme-linked immunosorbent assay (ELISA). IL-36α, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19 and expression in MSGs was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and tissue IL-36α and IL-38 expression was also investigated by immunohistochemistry (IHC). αβ and γδ T cells and CD68(+) cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. IL-36α was over-expressed significantly in the serum and in the salivary glands of pSS. Salivary gland IL-36α expression was correlated with the expression levels of IL-17, IL-22 and IL-23p19. IL-38, that acts as inhibitor of IL-36α, was also up-regulated in pSS. αβ(+) CD3(+) T cells and CD68(+) cells were the major source of IL-36α in minor salivary glands of pSS. γδ T cells were not significantly expanded in the salivary glands of pSS but produced more IL-17, as their percentage correlated with the focus score. Higher expression of IL-36α and IL-36R was also demonstrated in γδ T cells isolated from pSS compared to controls. In this study we demonstrate that a significant increase in circulating and tissue levels of IL-36α occurs in pSS patients.

Keywords: IL-36a; IL-38; IL36RA; Sjögren's syndrome; γδ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Case-Control Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-23 Subunit p19 / genetics
  • Interleukin-23 Subunit p19 / immunology
  • Interleukins / genetics
  • Interleukins / immunology
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology*
  • Salivary Glands / immunology*
  • Salivary Glands / pathology
  • Signal Transduction
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • IL-38 protein, human
  • IL36A protein, human
  • Interleukin-1
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • Interleukins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin
  • interleukin-36 receptor, human
  • interleukin-22