scholarly journals Inhibition of lysophosphatidic acid receptor ameliorates Sjögren's syndrome in NOD mice

Oncotarget ◽  
2017 ◽  
Vol 8 (16) ◽  
pp. 27240-27251 ◽  
Author(s):  
Eunhye Park ◽  
Donghee Kim ◽  
Song Mi Lee ◽  
Hee-Sook Jun
Keyword(s):  
Sjögren’S Syndrome ◽  
Lysophosphatidic Acid ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Sjögren‘S Syndrome

AB0062 Alteration of Tibial Metaphysis Area in NOD Mice Whit Sjögren's Syndrome

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 918.1-918
Author(s):  
C.A. Gobbi ◽  
B. Busamia ◽  
M.B. Guglielmotti ◽  
S. Fontana ◽  
M.C. Mariani ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Tibial Metaphysis ◽  
Sjögren‘S Syndrome

scholarly journals Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren’s Syndrome-Like Disease

2019 ◽  
Vol 20 (19) ◽  
pp. 4750 ◽  
Author(s):  
Ghada Abughanam ◽  
Osama A. Elkashty ◽  
Younan Liu ◽  
Mohammed O. Bakkar ◽  
Simon D. Tran
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Peripheral Tolerance ◽  
Lacrimal Glands ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is an autoimmune disease that manifests primarily in salivary and lacrimal glands leading to dry mouth and eyes. Unfortunately, there is no cure for SS due to its complex etiopathogenesis. Mesenchymal stem cells (MSCs) were successfully tested for SS, but some risks and limitations remained for their clinical use. This study combined cell- and biologic-based therapies by utilizing the MSCs extract (MSCsE) to treat SS-like disease in NOD mice. We found that MSCsE and MSCs therapies were successful and comparable in preserving salivary and lacrimal glands function in NOD mice when compared to control group. Cells positive for AQP5, AQP4, α-SMA, CK5, and c-Kit were preserved. Gene expression of AQP5, EGF, FGF2, BMP7, LYZ1 and IL-10 were upregulated, and downregulated for TNF-α, TGF-β1, MMP2, CASP3, and IL-1β. The proliferation rate of the glands and serum levels of EGF were also higher. Cornea integrity and epithelial thickness were maintained due to tear flow rate preservation. Peripheral tolerance was re-established, as indicated by lower lymphocytic infiltration and anti-SS-A antibodies, less BAFF secretion, higher serum IL-10 levels and FoxP3+ Treg cells, and selective inhibition of B220+ B cells. These promising results opened new venues for a safer and more convenient combined biologic- and cell-based therapy.

scholarly journals AB0131 RESPIRATORY TRACT POLY(I:C) STIMULATION ACCELERATES SALIVARY GLAND IMMUNE DYSFUNCTION IN SPONTANEOUS SJOGREN’S SYNDROME ANIMAL MODEL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1366.1-1367
Author(s):  
P. Hu ◽  
B. Ming ◽  
X. Wu ◽  
L. Dong
Keyword(s):  
Salivary Gland ◽  
Respiratory Tract ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Poly I:C ◽  
Interleukin 33 ◽  
Sjögren‘S Syndrome

Background:Sjogren’s syndrome is one of the most common autoimmune diseases, with a prevalence of 0.33% to 0.77% in Chinese people, characterized by focal infiltration of lymphocytes in glands and the production of multiple autoantibodies. Studies have shown that virus infection may play a crucial role in the occurrence and development of this disease.Objectives:It has been shown that airway stimulation with poly(I:C) can mimic respiratory tract viral infection to some extent. Thus, this study was aimed to investigate the dynamic immune responses in salivary gland after respiratory tract poly(I:C) stimulation in NOD mice.Methods:The 5-week-old NOD mice were given respiratory tract poly(I:C) stimulation to mimic the respiratory virus infection once every other day for a total of 5 times (the total dose is 100μg), and the control group were given the same dose of sterile PBS. After 8 weeks, the mice were sacrificed to obtain and analyze the salivary gland tissues.Results:We found that the salivary gland flow rate was decreased and the blood glucose was influenced by the Viroid stimulation during the early stage in poly(I:C) stimulated group compared with that in PBS group. Accordingly, the pathological injury of salivary gland tissues in poly(I:C) stimulated group was more serious, including decreased volumes of the salivary glands, increased number of pathological focus score and the increased area of lymphocyte infiltration. Furthermore, we found that the expression of IL-33 in salivary glands of poly(I:C) stimulated NOD mice was increased, especially the expression of IL-33 in the acini and ducts. Moreover, the expression of IFN-I and IFN-II is up-regulated in salivary glands.Conclusion:The results of this study suggest that respiratory tract poly(I:C) stimulation accelerates salivary gland immune dysfunction in spontaneous sjogren’s syndrome NOD mice, which mechanisms need to be further investigated.References:[1] Pathogenetic mechanisms in the initiation and perpetuation of Sjogren’s syndrome. Nat Rev Rheumatol 2010; 6: 529-537.[2]Primary Sjögren’s Syndrome. N Engl J Med.2018 378(10):931-939.[3]Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74: 1983-9.[4]Vitamin D insufficiency in a large MCTD population. Autoimmun Rev 10:317–324.[5]Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann Rheum Dis 72:1559–1568[6]Liew, F., Girard, J. & Turnquist, H. Interleukin-33 in health and disease. Nat Rev Immunol 16, 676–689 (2016) doi:10.1038/nri.2016.95[7]Interleukin-33 and the function of innate lymphoid cells. Trends in Immunology, August 2012, Vol. 33, No. 8[8]Increased Levels of Interleukin 33 in Sera and Synovial Fluid from Patients with Active Rheumatoid Arthritis YASUSHI MATSUYAMA et al The Journal of Rheumatology January 2010, 37 (1) 18-25[9]Potential involvement of the IL-33-ST2 axis in the pathogenesis of primary Sjogren’s syndrome, Ann Rheum Dis, 2014, 73(6): 1259-1263.[10]The Interleukin 33/ST2 axis in patients with primary Sjogren syndrome: expression in serum and salivary glands, and the clinical association, J Rheumatol, 2015, 42(2): 264-271.[11]Kok MR, Baum BJ, Tak PP, et al Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjögren’s syndrome Annals of the Rheumatic Diseases 2003;62:1038-1046.Acknowledgments:NODisclosure of Interests:None declared

IDD 3 AND IDD 5 ALLELES FROM NOD MICE MEDIATE SJÖGREN'S SYNDROME-LIKE AUTOIMMUNITY.

Cornea ◽  
2000 ◽  
Vol 19 (Supplement 2) ◽  
pp. S80
Author(s):  
S. Cha ◽  
H. Nagashima ◽  
J. Brayer ◽  
A. B. Peck ◽  
M. G. Humphreys-Beher
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status

2020 ◽  
Vol 598 (21) ◽  
pp. 4907-4925
Author(s):  
Yuta Ohno ◽  
Keitaro Satoh ◽  
Akiko Shitara ◽  
Takeshi Into ◽  
Masanori Kashimata
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Arginase 1 ◽  
Sjögren‘S Syndrome

scholarly journals THU0226 MESENCHYMAL STEM CELL TRANSPLANTATION AMELIORATES EXPERIMENTAL SJÖGREN’S SYNDROME BY DOWNREGUALTING MDSCS VIA COX2/PGE2 PATHWAY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.1-340
Author(s):  
G. Yao ◽  
S. Wang ◽  
L. Sun
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Suppressor Cells ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Myeloid Derived Suppressor Cells ◽  
Sjögren‘S Syndrome

Background:Although mesenchymal stem cells (MSCs) transplantation have been demonstrated to be an effective therapeutic approach to treat experimental Sjögren’s syndrome (ESS)1, the specific underlying mechanisms remain to be elucidated. Myeloid-derived suppressor cells (MDSCs) were significantly increased with decreased suppressive capacity during disease development in ESS2-3. However, the therapeutic effects and mechanisms by which MSCs regulating MDSCs in SS still remain unknown.Objectives:Here we aim to explore whether regulation of MDSCs was responsible for the beneficial effects of MSC transplantation on SS.Methods:The MSCs were infused intonon-obese diabetic (NOD) mice via the tail vein. The histological features of submandibular glands, lung, saliva flow rate were evaluated. The number and immune-suppressive activity of MDSCs, the subsets of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs) and monocytic-MDSCs (M-MDSCs) in NOD mice were determined. The bone marrow cells under MDSCs differentiation conditions were co-cultured with or without MSCs. The COX2 inhibitor NS-398, anti-TGF-β1, or anti-IFN-β antibodies were added to coculture medium of MSCs and MDSCs induced from bone marrow cells respectively.Results:We found that MDSCs in bone marrow and peripheral blood increased in ESS mice. MSC transplantation ameliorated SS-like syndrome and down-regulated the percentages of MDSCs, PMN-MDSCs and M-MDSCs and promoted their suppressive ability in ESS mice significantly (Figure 1). In vitro, MSCs could down-regulate the differentiation and up-regulate the suppressive ability of MDSCs. Mechanistically, MSCs inhibited the differentiation of MDSCs and PMN-MDSCs via secreting prostaglandin E2, and inhibited the differentiation of M-MDSCs by secreting interferon-β (Figure 2).Figure 1.MSCs ameliorated SS symptoms and decreased MDSCs in NOD mice.Figure 2.MSCs inhibited the differentiation of PMN-MDSCs and M-MDSCs by COX2/PGE2 and IFN-β respectively.Conclusion:Our findings suggested that MSCs alleviated SS-like symptoms by suppressing the aberrant accumulation and improving the suppressive function of MDSCs in ESS mice via COX2/PGE2 pathway.References:[1]Shi B, Qi J, Yao G, et al. Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells. Stem Cell Res Ther, 2018; 9(1):308.[2]Qi J, Li D, Shi G, et al. Myeloid-derived suppressor cells exacerbates Sjögren’s syndrome by inhibiting Th2 immune responses. Mol Immunol, 2018; 101:251-258.[3]Tian J, Rui K, Hong Y, et al. Increased GITRL impairs the function of myeloid-derived suppressor cells and exacerbates primary Sjögren’s syndrome. J Immunol, 2019; 202(6):1693-1703.Disclosure of Interests:None declared

Blockade of CD40–CD154 pathway interactions suppresses ectopic lymphoid structures and inhibits pathology in the NOD/ShiLtJ mouse model of Sjögren’s syndrome

2019 ◽  
Vol 78 (7) ◽  
pp. 974-978 ◽  
Author(s):  
Grazyna Wieczorek ◽  
Marc Bigaud ◽  
Sabina Pfister ◽  
Melanie Ceci ◽  
Katriona McMichael ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Nod Mice ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoantibody Production ◽  
Aqp5 Expression ◽  
Leucocyte Infiltration ◽  
Sjögren‘S Syndrome

ObjectiveTo examine the role of CD40–CD154 costimulation and effects of therapeutic pathway blockade in the non-obese diabetic (NOD/ShiLtJ) model of Sjögren’s syndrome (SS).MethodsWe assessed leucocyte infiltration in salivary glands (SGs) from NOD/ShiLtJ mice by immunohistochemistry and examined transcriptomics data of SG tissue from these animals for evidence of a CD40 pathway gene signature. Additionally, we dosed MR1 (anti-CD154 antibody) in NOD mice after the onset of SS-like disease and examined the effects of MR1 treatment on sialadenitis, autoantibody production, SG leucocyte infiltration, gene expression downstream of CD40 and acquaporin 5 (AQP5) expression.ResultsWe could detect evidence of CD40 expression and pathway activation in SG tissue from NOD mice. Additionally, therapeutic treatment with MR1 suppressed CD40 pathway genes and sialadenitis, inhibited ectopic lymphoid structure formation and autoantibody production, as well as decreased the frequency of antibody-secreting cells in SGs but had minimal effects on AQP5 expression in NOD/ShiLtJ SGs.ConclusionCD40–CD154 interactions play an important role in key pathological processes in a mouse model of SS, suggesting that blockade of this costimulatory pathway in the clinic may have beneficial therapeutic effects in patients suffering from this autoimmune exocrinopathy.

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