scholarly journals Fibroblasts in Sjögren’s Syndrome

2021 ◽  
Author(s):  
Kerstin Klein
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Severe Disease ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Lymphoid Structures ◽  
Salivary Gland Epithelial Cells ◽  
Sjögren‘S Syndrome

The Sjögren’s syndrome is an autoimmune disease characterized by chronic inflammation of the exocrine glands, leading to dryness of mucosal surfaces, and often to severe systemic manifestations. Here, the immunomodulatory function of fibroblasts derived from salivary glands, a primary site affected by the Sjögren’s syndrome, is discussed. Specific subsets of these fibroblasts drive the formation of tertiary lymphoid structures, which are associated with severe disease and which constitute a risk factor for the development of lymphoma in Sjögren’s syndrome. Single cell RNA-sequencing has provided new insights into subsets of fibroblasts in inflamed salivary glands and has provided evidence for the existence of shared inflammation-associated fibroblasts across chronically inflamed tissues. These findings support the concept of targeting the fibroblast compartment in Sjögren’s syndrome and other chronic inflammatory diseases. In addition to the immunomodulatory role of fibroblasts, the interaction of the epithelium with fibroblasts is essential for salivary gland homeostasis. Fibroblasts provide essential signals for the regeneration of salivary gland epithelial cells, which is disturbed in Sjögren’s syndrome, and leading to the loss of saliva secreting cells and subsequent hyposalivation.

scholarly journals Cenerimod, a selective S1P1 receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren’s syndrome

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Estelle Gerossier ◽  
Saba Nayar ◽  
Sylvie Froidevaux ◽  
Charlotte G. Smith ◽  
Celine Runser ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Mouse Model ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Clinical Parameters ◽  
Lymphoid Structures ◽  
Sjögren‘S Syndrome

Abstract Background Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren’s syndrome. Methods Cenerimod was administered in two established models of Sjögren’s syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test. Results In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands. Conclusions Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren’s syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.

AB0053 Ikba regulatory protein is downregulated in sjögren’s syndrome salivary gland epithelial cells.

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A801.3-A801
Author(s):  
M. D’amore ◽  
S. Lisi ◽  
R. De Lucro ◽  
D. Ribatti ◽  
M. Sisto
Keyword(s):  
Salivary Gland ◽  
Epithelial Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Regulatory Protein ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Salivary Gland Epithelial Cells ◽  
Sjögren‘S Syndrome

Androgens and Integrins in Salivary Glands in Sjögren’s Syndrome

2010 ◽  
Vol 37 (6) ◽  
pp. 1181-1187 ◽  
Author(s):  
PAULIINA POROLA ◽  
MIKAEL LAINE ◽  
ISMO VIRTANEN ◽  
RAIMO PÖLLÄNEN ◽  
BEATA D. PRZYBYLA ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Messenger Rna ◽  
Sjögren's Syndrome ◽  
Acinar Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mrna Levels ◽  
Sjögren‘S Syndrome

Objective.Laminin α1-chain normally induces intercalated duct progenitors to differentiate to acinar cells through integrin (INT) α1ß1 and α2ß1 receptors. Maintenance of acinar cells is impaired in Sjögren’s syndrome (SS), which is also characterized by low levels of serum and salivary androgens. We hypothesized that androgens normally support salivary gland remodeling by upregulating either laminin α1 chain or its cellular α1 or α2 INT subunit-containing receptors.Methods.Intercalated duct and acinar human salivary gland (HSG) cells and labial salivary gland (LSG) biopsies from healthy controls and patients with SS were cultured without or with sex steroids. Laminin α1 chain and INT α1 and α2 subunits were studied using quantitative reverse-transcription real-time polymerase chain reaction and INT α1 and α2 subunits using immunofluorescence staining.Results.INT α1-subunit and α2-subunit messenger RNA (mRNA) levels were increased in intercalated duct and acinar cells by DHEA and testosterone. In contrast, laminin α1-chain mRNA levels were not affected. The upregulating effect of DHEA on INT subunits was also seen at the protein level. DHEA also increased mRNA levels of both INT subunits in healthy but not SS LSG.Conclusion.Androgens increased INT α1 and α2 subunits in tubuloepithelial cells and in healthy LSG, but in SS salivary glands this androgen regulation was defective, which is likely to contribute to defective outside-in signaling, acinar atrophy, and ductal cell hyperplasia.

scholarly journals Skewed Production of IL-6 and TGFβ by Cultured Salivary Gland Epithelial Cells from Patients with Sjögren's Syndrome

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e45689 ◽  
Author(s):  
Takafumi Kawanami ◽  
Toshioki Sawaki ◽  
Tomoyuki Sakai ◽  
Miyuki Miki ◽  
Haruka Iwao ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Epithelial Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Salivary Gland Epithelial Cells ◽  
Sjögren‘S Syndrome

Lacrimal and Salivary Gland Inflammation in the C3H/lpr Autoimmune Strain Mouse: A Potential Mode for Sjögren's Syndrome

1992 ◽  
Vol 106 (4) ◽  
pp. 394-399 ◽  
Author(s):  
Ilsa Schwartz ◽  
Bruce C. Johnson ◽  
Jane I. Morton ◽  
Dennis R. Trune
Keyword(s):  
Salivary Gland ◽  
Autoimmune Disease ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Lacrimal Gland ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Systemic Autoimmune Disease ◽  
Sjögren‘S Syndrome

Sjögren's syndrome is an autoimmune inflammatory disease that affects the lacrimal and salivary glands. To identify a potential animal model for study of Sjögren's syndrome, an evaluation was made of lacrimal and salivary glands in the C3H/ lpr autoimmune strain mouse at ages before (2 months) and after (5 months) systemic autoimmune disease onset at 3 to 4 months. Quantitative and qualitative analyses of, C3H/ lpr lacrimal and salivary (parotid, submandibular, and sublingual) gland histopathology were performed using age-matched C3H/HeJ nonautoimmune mice to control for inflammation of nonautoimmune origin. No lacrimal or salivary gland inflammation was seen in either of the strains at 2 months of age and measures of systemic autoimmune disease were negative. At 5 months of age, the nonautoimmune C3H/HeJ controls showed a slight increase in lacrimal gland inflammation, but this was not significantly different from the 2 month old controls. A significant increase in lacrimal gland inflammation was found in the 5 month old C3H/ lpr autoimmune mice in a histologic pattern similar to that of Sjögren's syndrome in human beings. Furthermore, the degree of inflammation was positively correlated with serum immune complexes and spleen weight. Sporadic inflammation of the submandibular gland was seen in both autoimmune and control mice, but this was neither statistically significant nor correlated with measures of autoimmunity. No significant inflammation was seen in the parotid or sublingual glands.

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