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

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