scholarly journals Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren’s Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bo Hai ◽  
Taeko Shigemoto-Kuroda ◽  
Qingguo Zhao ◽  
Ryang Hwa Lee ◽  
Fei Liu
Keyword(s):  
Mouse Model ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Extracellular Vesicles ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Bioactive Molecules ◽  
Lymphocyte Infiltration ◽  
Sjögren‘S Syndrome

No effective treatment for Sjögren’s syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.

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.

scholarly journals Dysfunction of Lacrimal and Salivary Glands in Sjögren's Syndrome: Nonimmunologic Injury in Preinflammatory Phase and Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Toshiharu Hayashi
Keyword(s):  
Mouse Model ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Autoimmune Disorder ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Dry Eyes ◽  
Morphologic Changes ◽  
Sjögren‘S Syndrome

Sjögren's syndrome (SjS) is a chronic autoimmune disorder characterized by dry eyes and dry mouth due to dacryoadenitis and sialoadenitis with SS-A/Ro and/or SS-B/La autoantibodies in genetically predisposed individuals. Destruction of lacrimal and salivary glands by autoimmune reactions may lead to clinical manifestation. However, the mechanisms behind the decreased volume of secretions in tears and saliva are complex and are not fully understood. Exocrine gland dysfunction may precede autoimmunity (acquired immunity) or represent a process independent from inflammation in the pathogenesis of SjS. The preceded functional and morphologic changes of those tissues by nonimmunologic injury before the development of inflammation at the sites of target organs have been implicated. This paper focuses on the several factors and components relating to glandular dysfunction and morphologic changes by nonimmunologic injury during the preinflammatory phase in mouse model, including the factors which link between innate immunity and adaptive immunity.

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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