Interleukin-17 and -22 synergy linking inflammation and EMT-dependent fibrosis in Sjögren's syndrome. (5th June 2019)

• Record Type: Journal Article
• Authors: Sisto, M; Lorusso, L; Tamma, R; Ingravallo, G; Ribatti, D; Lisi, S
• Is Part Of: Clinical and experimental immunology. Volume 198:Number 2(2019)
• Page Start: 261
• Page End: 272
• Publication Date: 2019-06-05
• Subjects: EMT -- fibrosis -- interleukin -- salivary glands -- Sjögren's syndrome; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13337
• Languages: English
• ISSNs: 0009-9104

Abstract

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. Graphical Abstract: