OBJECTIVES: To investigate the expression of IL-36 axis in patients with primary Sjogren's syndrome (pSS). METHODS: Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 nSS patients. Serum IL-36α was assayed by ELISA. IL-36α, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19, expression in MSGs was assessed by rt-PCR and tissue IL-36α and IL-38 expression also investigated by immuno-histochemistry (IHC). αβ and γδ T cells and CD68+ cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. RESULTS: IL-36α was significantly over-expressed 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 being 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. CONCLUSIONS: in this study we demonstrate that a significant increase in circulating and tissue levels of IL-36α occurs in pSS patients.