Interleukin‐17 and ‐22 synergy linking inflammation and EMT‐dependent fibrosis in Sjögren’s syndrome

Summary Primary Sjögren’s syndrome (pSS) is a chronic inflammatory, autoimmune and systemic disorder commonly associated with dry eyes and a dry mouth. Recently, the hypothetical link between epithelial–mesenchymal transition (EMT)‐dependent salivary gland (SG) fibrosis and chronic inflammatory conditions has been suggested. In this study, we present data demonstrating a negative correlation of the epithelial marker E‐cadherin expression and a positive correlation of mesenchymal vimentin and collagen type I expression with increasing degrees of tissue inflammation in pSS SG specimens. In addition, as it is not clear whether dysregulated cytokines in pSS, interleukin (IL)‐17 and IL‐22 may also contribute to the EMT‐dependent fibrosis process, the effect of IL‐17 and IL‐22 treatment on EMT‐dependent SG fibrosis was evaluated in primary human salivary gland epithelial cells (SGEC) isolated from healthy subjects. Here we present data demonstrating that IL‐17 and IL‐22 can induce SGEC to undergo a morphological and phenotypical transition to a mesenchymal phenotype. In support of this, vimentin and collagen type I were up‐regulated while a decreased expression of E‐cadherin occurs after interleukin treatment, and co‐operation between IL‐17 and Il‐22 was required to induce the EMT.