Expression of BAFF(BLyS) in T cells infiltrating labial salivary glands from patients with Sjögren's syndrome

2004 ◽  
Vol 202 (4) ◽  
pp. 496-502 ◽  
Author(s):  
Frédéric Lavie ◽  
Corinne Miceli-Richard ◽  
Jeanine Quillard ◽  
Sophie Roux ◽  
Philippe Leclerc ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2302
Author(s):  
Mie Kurosawa ◽  
Yosuke Shikama ◽  
Masae Furukawa ◽  
Rieko Arakaki ◽  
Naozumi Ishimaru ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Aged Mice ◽  
Sjögren‘S Syndrome

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4+ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.

scholarly journals POS0776 CORRELATION OF PERIPHERAL CD4+GRANZB+CTLS WITH DISEASE SEVERITY IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.3-642
Author(s):  
Q. Wang ◽  
L. Gu ◽  
M. Zhang
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Sjögren’S Syndrome ◽  
Mhc Class Ii ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Extraglandular Manifestations ◽  
Sjögren‘S Syndrome

Background:Sjögren’s syndrome (SS) is a chronic autoimmune disorder. The major histopathologic lesion of it is a focal lymphocytic infiltrate around ductal and acinar epithelial cells, which include a majority of CD4+T. Several studies have shown that the epithelial cells in SS present diverse phenomena, such as MHC class II overexpression. CD4+T cells with cytotoxic activity (CD4 CTL) have been detected in various immune responses. They are characterized by their ability to secrete perforin and granzyme B to kill the target cells in an MHC class II-restricted fashion.Objectives:So this study was to investigate the correlation of peripheral CD4+GranzB+CTLs with disease severity and organ involvement in patients with primary Sjögren’s syndrome.Methods:We recruited 116 pSS patients and 46 healthy controls using flow cytometry to examine proportion of CD4+GranzB+CTLs in their peripheral blood, and immunofluorescence to test the expression of CD4+GranzB+CTLs in labial gland. The correlations of CD4+GranzB+CTLs and the relevant clinical data were analyzed.Results:We analyzed the percentage of CD4+GranzB+cytotoxic T cells in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Frequency of peripheral CD4+GranzB+CTLs were measured in 116 patients with pSS and 46 healthy controls matched for age and sex. The percentage of CD4+GranzB+CTLs were significantly up-regulated in pSS patients than healthy controls (7.1%±4.9% vs 3.1%±1.9%, p <0.0001) and positive correlation with ESSDAI in pSS patients(r = 0.6332, p<0.001). The percentage of CD4+GranzB+CTLs were markedly higher in pSS patients with extraglandular manifestations. Moreover, CD4+GranzB+CTLs were observed in the lymphocytic foci and periductal areas of the LSGs and were elevated with increased foci index (FI). After excluding the other risk factors associated with pSS, CD4+GranzB+CTLs were still related to ESSDIA and extraglandular manifestations independently(p<0.05). ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS, and 0.851 to presume extraglandular manifestations. The best diagnostic cut-off point was 4.865 for pSS patients.Conclusion:In this study, We provide new evidence indicating involvement of CD4+GranzB+CTLs over activation in the disease pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.References:[1]Takeuchi A, Saito T. Front Immunol. (2017) 23:194.[2]Brown DM, et al. Front Immunol. (2016) 9:93.[3]Polihronis M, et al. Clin Exp Immunol. (1998) 114:485-90.[4]Xanthou G, et al. Clin Exp Immunol. (1999) 118:154-63.[5]Maehara T, et al. Ann Rheum Dis. (2017) 76:377-385.[6]Goules AV, et al. Clin Immunol. (2017) 182:30-40.[7]Hashimoto K, et al. Proc Natl Acad Sci U S A. (2019) 116:24242-24251.[8]Croia C, et al. Arthritis Rheumatol. (2014) 66:2545-57.[9]Schmidt D,et al. J Clin Invest. (1996) 97:2027–37.[10]Pandya JM, et al. Arthritis Rheum. (2010) 62:3457–66.[11]Moosig F, et al. Clin Exp Immunol. (1998) 114:113–8.[12]Peeters LM, et al. Front Immunol. (2017) 20:1160.Table 1.Multivariate analysis of CD4+GranzB+CTLs influenced by pSS-related factorsregression coefficientstandard errort-statisticsp value95%CICD8+GranzB+CTLs(%)0.1440.0334.3346.9E-50.077, 0.211ESSDAI0.2560.1222.0950.0410.011, 0.502extraglandular manifestations2.6121.2682.0590.0450.065, 5.158Figure 1.Receiver operating characteristic (ROC) curve of the frequency of CD4+GranzB+CTLs to predict ESSDAI and extraglandular manifestations responseDisclosure of Interests:None declared

Activation of MKK4 (SEK1), JNK, and c-Jun in labial salivary infiltrating T cells in patients with Sjögren’s syndrome

2006 ◽  
Vol 27 (4) ◽  
pp. 329-333 ◽  
Author(s):  
Kazutaka Soejima ◽  
Hideki Nakamura ◽  
Mami Tamai ◽  
Atsushi Kawakami ◽  
Katsumi Eguchi
Keyword(s):  
T Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

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.

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