scholarly journals Emerging Role of microRNAs and Long Non-Coding RNAs in Sjögren’s Syndrome

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 903
Author(s):  
Giada De Benedittis ◽  
Cinzia Ciccacci ◽  
Andrea Latini ◽  
Lucia Novelli ◽  
Giuseppe Novelli ◽  
...  

Sjögren’s Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic regulations represent a link between genetic predisposition and environmental factors. Recent studies suggested a regulatory role for non-coding RNAs in critical biological and disease processes. Among non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a critical role in the post-transcriptional mRNA expression, forming a complex network of gene expression regulation. This review aims to give an overview of the latest studies that have investigated the role of miRNAs and lncRNAs in the SS. We included papers that investigated the expression of non-coding RNAs on different tissues, in particular on peripheral blood mononuclear cells and salivary glands. However, regarding the involvement of non-coding RNAs genetic variability in SS susceptibility very few data are available. Further research could help to elucidate underlying pathogenic processes of SS and provide new opportunities for the development of targeted therapies.

2014 ◽  
Vol 74 (6) ◽  
pp. 1302-1310 ◽  
Author(s):  
Xiang Lin ◽  
Ke Rui ◽  
Jun Deng ◽  
Jie Tian ◽  
Xiaohui Wang ◽  
...  

ObjectiveAlthough Th17 cells have been increasingly recognised as an important effector in various autoimmune diseases, their function in the pathogenesis of Sjögren's syndrome (SS) remains largely uncharacterised. This study aims to determine the role of Th17 cells in the development of experimental SS (ESS).MethodsThe ESS was induced in wildtype and IL-17A knockout (IL-17 KO) C57BL/6 mice immunised with salivary glands (SG) proteins. Phenotypic analysis of immune cells in the draining cervical lymph nodes (CLN) and SG was performed by flow cytometry and immunofluorescence microscopy. To determine the role of Th17 cells in ESS, immunised IL-17 KO mice were adoptively transferred with in vitro-generated Th17 cells and monitored for SS development. The salivary flow rate was measured, whereas inflammatory infiltration and tissue destruction in SG were assessed by histopathology.ResultsSG protein-immunised mice developed overt SS symptoms with increased Th17 cells detected in CLN and within lymphocytic foci in inflamed SG. Notably, immunised IL-17 KO mice were completely resistant for SS induction, showing no evidence of disease symptoms and histopathological changes in SG. Adoptive transfer of Th17 cells rapidly induced the onset of ESS in immunised IL-17 KO mice with markedly reduced saliva secretion, elevated autoantibody production and pronounced inflammation and tissue damage in SG.ConclusionsOur findings have defined a critical role of Th17 cells in the pathogenesis of ESS. Further studies may validate Th17 cell as a potential target for treating SS.


2014 ◽  
Vol 194 (1) ◽  
pp. 56-67 ◽  
Author(s):  
Mana Iizuka ◽  
Hiroto Tsuboi ◽  
Naomi Matsuo ◽  
Hiromitsu Asashima ◽  
Tomoya Hirota ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Weiqian Chen ◽  
Jin Lin ◽  
Heng Cao ◽  
Danyi Xu ◽  
Bei Xu ◽  
...  

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren’s syndrome (pSS). The inhibitor ofκB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/εin patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε(pIKKε), pIκBα, and pNF-κB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKα/βand pIKKγwere both negative. And pIKKεpositively related to expression of p-p65. Furthermore, pIKKεand p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKε, total IKKε, pIKKα/β, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKγand IκBαbetween pSS patients and healthy individuals. These results demonstrated an abnormality of IKKε, IκBα, and NF-κB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKεexpression and deregulation of NF-κB pathway.


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