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

Abstract

Summary 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.

Analysis of Clinical Characteristics of Immune-Related Dry Eye

“…This showed that the ocular surface inflammatory reaction of this kind of patients was more serious than that of simple dry eye [19–23]. In this study, we also found that corneal nerve fibers were less and the number of local lymphocytes was significantly increased in IRDE than those in SDE by confocal microscopy scan.…”

Biology of IL‐38 and its role in disease

“…Moreover, risk of renal and central nervous system involvement was directly correlated with IL‐38 serum levels, and higher detectable baseline levels of IL‐38 in the circulation increased the risk of persistent active disease . A disease related to SLE is Sjogren's disease in which the expression of IL‐38 was found to be upregulated in gland biopsies from patients with primary Sjogren's disease . The IL‐36 axis was proposed in this study to be important for disease modulation in Sjogren, and with IL‐38 being a possible antagonist of IL‐36 signaling similar to IL‐36Ra it might play a significant role in the pathogenesis of this autoimmune disease …”

Overview of the IL‐1 family in innate inflammation and acquired immunity

“…In keratinocytes, blocking IL‐36γ with siRNA or IL‐36 receptor suppressed LL37‐mediated production of IL‐8 as well as CXCL10 . Elevated circulating levels as well as salivary glands of IL‐36a have been reported in patients with Sjogren's syndrome . Histologically, α/β and γ/δ T cells were identified in the salivary glands of the patients.…”