scholarly journals AB0035 TWO DIFFERENT ABNORMAL BEHAVIORS IN CD4+T LYMPHOCYTES IN FIBROMYALGIA PATIENTS AND FIBROMYALGIA ASSOCIATED TO SJÖGREN’S SYNDROME

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1320-1321
Author(s):  
J. Monserratsanz ◽  
A. Movasat ◽  
M. D. Sosa Reina ◽  
A. M. Gomez Lahoz ◽  
C. Bohórquez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Sjögren’S Syndrome ◽  
Cd4 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Fibromyalgia ◽  
Sjögren‘S Syndrome

Background:Primary fibromyalgia syndrome is a prevalent rheumatic condition characterized by widespread pain and whose etiopathogenesis is not well understood. Fibromyalgia can also be secondary to other rheumatic diseases like Sjogren’s syndrome; however, its relation to this disease is unknown. It has been suggested that the immune system is involved in their pathogenesis. The role of activation stages and cytokines profiles of CD4+T lymphocytes in fibromyalgia or fibromyalgia secondary to Sjogren´s syndrome are completely unclear and could play a key role in the pathophysiology of these diseases.Objectives:The objective of this study is to investigate the counts and distribution of the CD4+T lymphocyte activation subsets and their pattern of cytokine production in women with primary fibromyalgia, fibromyalgia secondary to Sjogren´s, Sjogren´s syndrome and healthy controls (HC). The counts and distribution of naïve (TN), central memory (TCM), effector memory (TEM) and effector (TE) CD4+T lymphocyte subsets were analyzed in these diseases. Furthermore, we investigated their pattern of IL-4, IL-10, IL-17A, IFNγ, and TNFα production.Methods:Counts and distribution of CD4+T subsets (TN, TCM, TEM, TE)and their cytokine producing capacity were measured using multiparametric flow cytometry in peripheral blood mononuclear cells (PBMC) from 20 primary fibromyalgia, 15 fibromyalgia associated to Sjögren and 15 primary Sjögren patients and 15 female controls. Fibromyalgia and/or Sjögren’s syndrome were diagnosed based on ACR criteria. CD4+T cell activation stages were analyzed by the expression of the CD3, CD4, CD45RA, CD27 and CCR7 antigens. Cytokine CD4+T producing cells subsets were assayed stimulating PBMC during 6 hours, fixed, permeabilized and simultaneously stained with IL-4, IL-10, IL-17A, IFNγ, and TNFα intracellular cytokines.Results:Fibromyalgia patients showed a significant increase in the CD4+T, TNand TCMcells counts with compared to fibromyalgia secondary to Sjogren, Sjogren´s syndrome and HC. The counts of IL-17A, IL-4 and IFNγ producing CD4+T cells were increased in fibromyalgia patients with respect to HC. However, only IL17A and IFNγ, but not IL-4 producing CD4+T lymphocytes were increased with respect fibromyalgia secondary to Sjogren. These alterations were due to an increment of TEMIL-17A, TCMand TEMIL-4 and TNTCMand TEMIFNγ producing CD4+T cell subsets in fibromyalgia patients. Furthermore, IFNγ producing CD4+T cells were decreased in fibromyalgia secondary to Sjogren´s with respect to fibromyalgia patients and HC. Counts of TNTNFα producing CD4+ T cells were increased in fibromyalgia with respect fibromyalgia secondary to Sjogren. IL-10 producing CD4+T cells were normal in fibromyalgia but decreased in fibromyalgia secondary to Sjogren.Conclusion:Fibromyalgia patients show an abnormal circulating activation stages of CD4+T cells, as well as, express unusual elevated counts of CD4+T cells producing IL-17A, IL-4 and IFNγ. These alterations could differentiate two different pathologic and inflammatory behaviors of the T cell compartment between fibromyalgia and fibromyalgia secondary to Sjogren patients.References:[1]T helper 1 response is correlated with widespread pain, fatigue, sleeping disorders and the quality of life in patients with fibromyalgia.. Guggino G et al, Clin Exp Rheumatol. 2019.[2]A Comparative Study of Fibromyalgia, Rheumatoid Arthritis, Spondyloarthritis, and Sjögren’s Syndrome. Bucourt E et al, Pain Med. 2019Disclosure of Interests:None declared

scholarly journals Development of autoimmune exocrinopathy resembling Sjögren's syndrome in adoptively transferred mice with autoreactive CD4+ T cells

2003 ◽  
Vol 48 (12) ◽  
pp. 3603-3609 ◽  
Author(s):  
Rieko Arakaki ◽  
Naozumi Ishimaru ◽  
Ichiro Saito ◽  
Masaru Kobayashi ◽  
Natsuo Yasui ◽  
...  
Keyword(s):  
T Cells ◽  
Sjögren’S Syndrome ◽  
Cd4 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoimmune Exocrinopathy ◽  
Sjögren‘S Syndrome

scholarly journals T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1539
Author(s):  
William de Jesús Ríos-Ríos ◽  
Sorely Adelina Sosa-Luis ◽  
Honorio Torres-Aguilar
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Disease Progression ◽  
Sjögren’S Syndrome ◽  
Cd8 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different stages of the ailment, becoming involved in specific pathologic roles. Initially, their activated phenotype endows them with high migratory properties and increased pro-inflammatory cytokine secretion in target tissues. Later, the accumulation of immunomodulatory T cells-derived factors, such as IL-17, IFN-γ, or IL-21, preserve the inflammatory environment. These effects favor strong B cell activation, instigating an extrafollicular antibody response in ectopic lymphoid structures mediated by T follicular helper cells (Tfh) and leading to disease progression. Additionally, the memory effector phenotype of CD8+ T cells present in SS patients suggests that the presence of auto-antigen restricted CD8+ T cells might trigger time-dependent and specific immune responses. Regarding the protective roles of traditional regulatory T cells (Treg), uncertain evidence shows decrease or invariable numbers of circulating and infiltrating cells. Nevertheless, an emerging Treg subset named follicular regulatory T cells (Tfr) seems to play a critical protective role owing to their deficiency that enhances SS development. In this review, the authors summarize the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues, and that simultaneously make them key therapeutic targets for SS treatment.

scholarly journals Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 530
Author(s):  
Po-Chang Wu ◽  
Shih-Chao Lin ◽  
Lauren Panny ◽  
Yu-Kang Chang ◽  
Chi-Chien Lin ◽  
...  
Keyword(s):  
T Cells ◽  
Sjögren’S Syndrome ◽  
Cd4 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Herbal Formula ◽  
Chinese Herbal Formula ◽  
Chinese Herbal ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

scholarly journals POS0732 IDENTIFICATION OF AUTOPHAGY-RELATED PHENOTYPES IN PRIMARY SJOGREN’S SYNDROME

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 616.2-617
Author(s):  
R. Zhao ◽  
S. X. Zhang ◽  
J. Qiao ◽  
S. Song ◽  
Y. Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Gland ◽  
T Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Primary Sjögren’S Syndrome ◽  
Primary Sjogren’S Syndrome ◽  
Sjögren‘S Syndrome

Background:Primary Sjogren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by disorders of effector T cell subpopulations such as Th1, Th2, Th17, regulatory T cells, and follicular helper T cells 1 2. Autophagy is an evolutionarily conserved self-digestion process that plays an important role in T cell-mediated immune response3. The relationship between autophagy and T cell subsets was unclear in pSS up till now.Objectives:To landscape the autophagy-related multiple gene expression signature in pSS classification and discover the influence of autophagy in T cell subsets.Methods:Gene expression profiles of pSS samples (GSE66795, GSE51092, GSE154926) were acquired from GEO database. A set of significant G-ATGs were intersected from the global gene of patients and 232 autophagy genes (ATGs) which were obtained from the Human Autophagy Database (HADb, http://www.autophagy.lu/). In training dataset (GSE66795, including 155 patients and 29 healthy controls), non-negative matrix factorization was used to divided patients by G-ATGs expression microarray data. An autophagy score model divided patients into the high-autophagy score and low groups by ssGSEA scores of gene according to normalized G-ATGs training data. Further, new classifications were validated by both peripheral blood samples (GSE51092, 90 patients) and salivary gland tissue (GSE154926, 43 participants).Results:Two distinct subtypes were identified and validated by 206 selected significant G-ATGs in training datasets (figure 1A,B) and validation datasets according to the autophagy score (figure 1D,E,F) Combined with clinical information of salivary gland dataset, it was found that most patients with early pSS were grouped in the high autophagy, while advanced patients were grouped in the low (figure 1G). Patients in high-autophagy group had higher levels of Treg cells and Th2 cells but lower concentrations of Th17 and Th1 in peripheral blood (figure 1C, P <0.05). Similar results were also observed in salivary gland tissue (figure 1H, P <0.05).Conclusion:Patients with different autophagy status differs from each other. Autophagy is closely corelated with lymphocyte subpopulations in patients with pSS. This work may help inform therapeutic decision-making for the treatment of pSS.References:[1]Colafrancesco S, Vomero M, Iannizzotto V, et al. Autophagy occurs in lymphocytes infiltrating Sjögren’s syndrome minor salivary glands and correlates with histological severity of salivary gland lesions. Arthritis research & therapy 2020;22(1):238. doi: 10.1186/s13075-020-02317-6 [published Online First: 2020/10/15].[2]Alessandri C, Ciccia F, Priori R, et al. CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity. Arthritis research & therapy 2017;19(1):178. doi: 10.1186/s13075-017-1385-y [published Online First: 2017/07/27].[3]Wei J, Long L, Yang K, et al. Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis. Nature immunology 2016;17(3):277-85. doi: 10.1038/ni.3365 [published Online First: 2016/01/26].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals O31 IL-27 regulates the magnitude of ectopic germinal centres in experimental sialadenitis but fails to modulate IL-17 and IFNg production in CD4 T cells from patients with Sjögren's syndrome

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Davide Lucchesi ◽  
Rachel Coleby ◽  
Elena Pontarini ◽  
Edoardo Prediletto ◽  
Felice Rivellese ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Sjögren’S Syndrome ◽  
Cd4 T Cells ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Expression Levels ◽  
Cellular Source ◽  
Sjögren‘S Syndrome

Abstract Background A third of Sjögren’s syndrome (SS) patients develop ectopic lymphoid structures (ELS) in their salivary glands (SG). ELS play an active role in autoimmunity and contribute to the development of MALT lymphoma. Interleukin 27 (IL-27) exerts key immunomodulatory actions on numerous immune cells but its role in the formation and regulation of ELS in the SG of SS is unknown. Here we used a murine model of SG ELS to elucidate the role of IL-27 and its interaction with IL-17 in the development, regulation and function of ELS. We extended our observations on a cohort of SS patients to identify IL-27 cellular source, target cells and functional properties in modulating CD4 T cells function. Methods A single dose of reporter-encoding adenovirus was delivered directly to the SG of wild-type (WT) and IL-27RA-deficient (KO) mice to trigger ELS formation. For IL-17 blockade, anti-mouse IL-17A antibody was used. ELS development and peripheral immune responses were tracked by immuno-histopathology, FACS, and qPCR. Minor SG biopsies were collected from SS and non-specific sialadenitis (sicca) patients. Peripheral blood mononuclear cells (PBMC) isolated from SS and rheumatoid arthritis (RA) patients and age/sex-matched healthy donors (HD). For in vitro experiments PBMCs were incubated with IL-27 and analysed by FACS and cytokines levels were measured in culture supernatants. Tissue IL-27 was assessed by multicolour immunofluorescence. Results In WT mice, SG ELS formation was preceded by upregulation of IL-27p28 and infiltration of IL-27 producing cells. KO mice displayed larger, more abundant ELS in the SG. Higher expression levels of ELS-related genes (Cxcl13, Ccl19, Ltb, Aid) compared to WT mice were measured. KO mice showed an uncontrolled SG Th17 response and systemic IL-17A blockade caused a reduction in ELS size and in the expression of ELS-related genes. In SS patients SG and serum, we observed higher expression levels of IL-27 transcripts and protein, compared to sicca. SG IL-27 was selectively increased in ELS+ patients. IL-27 staining was detected in the T cell-rich areas of SG ELS often co-localizing with DC-LAMP+ dendritic cells. While IL-27 was able to significantly downregulate IL-17 production in HD and RA, CD4 T cells from patients with SS failed to downregulate IL-17 but showed an aberrant IFNγ release upon IL-27 incubation. Conclusion The IL-27-mediated restriction of Th17 expansion plays a critical role in the regulation of germinal centre response. Both in murine inducible ELS and in patients with SS, dendritic cells appear as the main cellular source of IL-27. IL-27 consistently failed to downregulate IL-17 release in CD4 T cells from SS patients, albeit its expression was increased in the ELS+ subset of SS, suggesting that a profound dysregulation of the IL-27/IL-17 axis play an important role in ELS formation in this condition. Disclosures D. Lucchesi None. R. Coleby None. E. Pontarini None. E. Prediletto None. F. Rivellese None. D. Hill None. A. Derrac Soria None. S. Jones None. I. Humphreys None. N. Sutcliffe None. A. Tappuni None. C. Pitzalis None. G. Jones None. M. Bombardieri None.

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