Th17 cells play a critical role in the development of experimental Sjögren's syndrome

2014 ◽  
Vol 74 (6) ◽  
pp. 1302-1310 ◽  
Author(s):  
Xiang Lin ◽  
Ke Rui ◽  
Jun Deng ◽  
Jie Tian ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Th17 Cells ◽  
Sjögren's Syndrome ◽  
Critical Role ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cervical Lymph Nodes ◽  
Autoantibody Production ◽  
Sjögren‘S Syndrome

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.

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 ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Sjögren’S Syndrome ◽  
Genetic Predisposition ◽  
Sjögren's Syndrome ◽  
Critical Role ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Non Coding Rnas ◽  
Sjögren‘S Syndrome

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.

scholarly journals A Crucial Role of RORγt in the Development of Spontaneous Sialadenitis-like Sjögren’s Syndrome

2014 ◽  
Vol 194 (1) ◽  
pp. 56-67 ◽  
Author(s):  
Mana Iizuka ◽  
Hiroto Tsuboi ◽  
Naomi Matsuo ◽  
Hiromitsu Asashima ◽  
Tomoya Hirota ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Crucial Role ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals TLR7 Signaling Drives the Development of Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yawen Wang ◽  
Annie Roussel-Queval ◽  
Lionel Chasson ◽  
Noël Hanna Kazazian ◽  
Laetitia Marcadet ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Autoimmune Disease ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoantibody Production ◽  
Deficient Mice ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased TLR7 expression levels compared to healthy individuals, that were positively correlated to TNF, LT-α, CXCL13 and CXCR5 expression. These findings establish an important role of TLR7 signaling for local and systemic SS disease manifestations, and inhibition of such will likely have therapeutic value.

scholarly journals STAT4, TRAF3IP2, IL10, and HCP5 Polymorphisms in Sjögren’s Syndrome: Association with Disease Susceptibility and Clinical Aspects

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Serena Colafrancesco ◽  
Cinzia Ciccacci ◽  
Roberta Priori ◽  
Andrea Latini ◽  
Giovanna Picarelli ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Variant Allele ◽  
Clinical Aspects ◽  
Autoantibody Production ◽  
Focus Score ◽  
Risk Alleles ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune condition characterized by autoantibody production, sicca syndrome, and periepithelial lymphocytic lesions in target tissues. A predisposing genetic background is likely, and, to date, several polymorphisms in non-HLA genes have been explored with interesting results. We investigated the association between the STAT4, TRAF3IP2, HCP5, and IL10 polymorphisms and SS susceptibility and their possible role in the modulation of clinical and laboratory features. 195 consecutive patients with SS were enrolled and clinical and laboratory data were collected. 248 age- and sex-matched healthy subjects were used as controls. Genotyping was performed by allelic discrimination assays. A case-control association study and a phenotype-genotype correlation analysis were performed. A genetic risk profile was developed considering the risk alleles. Both the variant alleles of rs7574865 in the STAT4 gene and rs3099844 in the HCP5 gene were significantly more prevalent in patients than in controls (OR=1.91 and OR=2.44, respectively). The variant allele of rs3024505 of IL10 resulted to be a susceptibility allele (OR=1.52), while the variant allele of rs1800872 seemed to confer a protective effect for the development of the disease (OR=0.65). A risk genetic profile showed a higher probability to develop the disease in subjects with at least three risk alleles; subjects with 4 risk alleles were not observed in the controls. HCP5 rs3099844 was associated with anti-SSA (P=0.006, OR=3.07) and anti-SSB (P=0.005, OR=2.66) antibodies, severity of focus score (P=0.03, OR=12), and lymphoma development (P=0.002, OR=7.23). Patients carrying the STAT4 rs7574965 variant allele had a higher risk of monoclonal component and leukopenia (P=0.002, OR=7.6; P=0.048, OR=2.01, respectively). We confirmed the association of SS with the STAT4 and IL10 genes and we describe a novel association with HCP5. In particular, we describe an association of this specific SNP of HCP5 not only with disease development but also with autoantibody production and focus score suggesting a potential contribution of this variant to a more severe phenotype.

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