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.

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.

scholarly journals Sjögren’s syndrome: a systemic autoimmune disease

2021 ◽  
Author(s):  
Simone Negrini ◽  
Giacomo Emmi ◽  
Monica Greco ◽  
Matteo Borro ◽  
Federica Sardanelli ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Autoimmune Disease ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoantibody Production ◽  
Sjögren‘S Syndrome

AbstractSjögren’s syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren’s syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren’s syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren’s syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren’s syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren’s syndrome, starting from its pathogenesis to current therapeutic options.

Levels of plasmacytoid dendritic cells and type-2 myeloid dendritic cells are reduced in peripheral blood of patients with primary Sjögren's syndrome

2009 ◽  
Vol 69 (6) ◽  
pp. 1235-1238 ◽  
Author(s):  
Petra Vogelsang ◽  
Johan G Brun ◽  
Gunnvor Øijordsbakken ◽  
Kathrine Skarstein ◽  
Roland Jonsson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Sjögren’S Syndrome ◽  
Peripheral Blood ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Myeloid Dendritic Cells ◽  
Antigen Presenting ◽  
Sjögren‘S Syndrome

ObjectiveSjögren's syndrome (SS) is a lymphoproliferative autoimmune disease, characterised by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells crucial for initiating and maintaining primary immune responses. This study quantified interferon-producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in peripheral blood (PB) from primary SS (pSS) patients and healthy controls.MethodsBlood samples from 31 pSS patients and 28 gender and age-matched healthy controls were analysed by flow cytometry using the Miltenyi Blood DC enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analysed by immunohistochemistry.ResultsPatients with pSS had significantly less pDC and mDC2 in PB compared with healthy controls. Moreover, pDC are present in SG from patients with pSS.ConclusionPatients with pSS have alterations among DC populations in PB, and pDC are present in the SG, suggesting a potential role of these cells in SS.

scholarly journals Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögren’s syndrome: findings in serum and minor salivary glands

Reumatismo ◽  
2016 ◽  
Vol 67 (3) ◽  
pp. 85 ◽  
Author(s):  
A. Alunno ◽  
V. Caneparo ◽  
F. Carubbi ◽  
O. Bistoni ◽  
S. Caterbi ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Minor Salivary Glands ◽  
Primary Sjogren’S Syndrome ◽  
Primary Sjögren's Syndrome ◽  
Sjögren‘S Syndrome

The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren’s syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD) by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs) of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.

Interdisciplinary approach to the management of a patient with Sjogren’s syndrome: a clinical case

2021 ◽  
Author(s):  
N. Y. Emelyanova ◽  
T. E. Kozyrieva ◽  
O. V. Stepanova ◽  
N. V. Zorenko
Keyword(s):  
Oral Cavity ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Clinical Case ◽  
Sjögren's Syndrome ◽  
Interdisciplinary Approach ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mucous Membranes ◽  
Sjögren‘S Syndrome

Dryness of the mucous membranes (in mouth, nose, genitals in women) and skin are the most common complaints of patients with Sjogren’s disease — a multisystem immune‑mediated disorder that causes anxiety and concern associated with the difficulties of initial diagnosis. The authors present a clinical case of a patient with primary Sjogren’s syndrome, a large number of symptoms of digestive diseases, complaints of dryness of mucous membranes, in particular the oral cavity. The diagnosis was confirmed by allied specialists such as ophthalmologist, gynecologist, rheumatologist, dentist. Detailed dental examination revealed the main dental complaints (constant dry mouth, galitos, changes in taste), clinical condition (dryness of the red border of the lips, swelling of the oral mucosa, changes in the relief of the gums), decreased secretory activity and significant reduction of unstimulated salivation with a moderate level of stimulated salivation. It is noted that a significant decrease in sialometry (0.01 ml per minute) and functional activity of the small salivary glands (up to 18) confirms the presence of true xerostomia. Micro‑crystallization of saliva revealed disorganization of irregularly shaped structures, as well as a significant number of organic inclusions, which indicates a violation of homeostasis in the oral cavity. Given the results of ultrasound examination of the large salivary glands and the absence of enlargement and swelling of the glands during clinical examination, we can assume that the destructive damage to the glands is not so pronounced, evacuation function of the gland is not reduced, but the amount of secretion is significantly reduced. To provide medical aid to patients with Sjogren’s syndrome, the accessibility of the qualified consultation is important and required, with conduction of comprehensive examinations by allied specialists, including a dentist.  

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