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 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 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 Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells

2021 ◽  
Author(s):  
Ke Rui ◽  
Yue Hong ◽  
Qiugang Zhu ◽  
Xiaofei Shi ◽  
Fan Xiao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Disease Progression ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Suppressor Cells ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Myeloid Derived Suppressor Cells ◽  
Sjögren‘S Syndrome

AbstractSjögren’s syndrome (SS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands. Our previous studies showed that myeloid-derived suppressor cells (MDSCs) exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome (ESS), but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS. In this study, we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels. Moreover, treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice. Mechanistically, OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs. In addition, the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling, indicating an autocrine pathway of MDSC functional modulation by IL-6. Taken together, our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs, possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.

Sign in / Sign up

Export Citation Format

Share Document