CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

Zhou, Huimin; Yang, Jun; Tian, Jie; Wang, Shengjun

doi:10.3389/fimmu.2020.602823

Cited by 43 publications

(39 citation statements)

References 136 publications

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“…Therefore, it is possible that the patients in the early stage with less lymphocytic infiltration have a different overview of immunopathogenesis. Although several studies reported the pathogenetic roles of CD8+ T cells, the involvement of CD8+ T cells in disease initiation remains to be further explored 56 – 59 .…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome

Kaneko

Chen

Perugino

et al. 2022

Sci Rep

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Sjögren’s syndrome is a chronic autoimmune disorder whose pathogenesis is poorly understood and that lacks effective therapies. Detailed quantitative and spatial analyses of tissues affected by Sjögren’s syndrome were undertaken, including the quantitation of the frequency of selected cell–cell interactions in the disease milieu. Quantitative analyses of CD4+ T cell subsets and of CD8+ T cells in the labial salivary glands from untreated patients with primary Sjögren’s syndrome revealed that activated CD8+ cytotoxic T cells (CD8+CTLs) were the most prominent T cells in these infiltrates. An accumulation of apoptotic glandular epithelial cells, mainly ductal and acinar cells, was observed, consistent with the impaired salivary secretion often observed in patients with this disease. FasL expressing activated CD8+ T cells were seen to accumulate around Fas expressing apoptotic epithelial cells. Quantitative analyses of apoptotic cell types and of conjugates between cytotoxic T cells and epithelial cells undergoing apoptosis suggest that Sjögren’s syndrome is primarily driven by CD8+CTL mediated execution of epithelial cells mainly represented by ductal and acinar cells.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome

Kaneko

Chen

Perugino

et al. 2022

Sci Rep

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“…Tfhs can promote secretion of proinflammatory cytokines in target tissues, such as IL-17 and IFN, participating in the specific pathological functions of different stages of SS development ( 24 , 25 ). Various studies have shown that CD8 + T lymphocytes also contribute to damage to exocrine acini ( 26 ). On the other hand, a large number of B cells proliferate and become activated in the salivary glands.…”

Section: Histopathological Features Of Salivary Glandsmentioning

confidence: 99%

Recent Advances of Salivary Gland Biopsy in Sjögren's Syndrome

Liao

Yang

et al. 2022

Front. Med.

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Sjögren's syndrome (SS) is a chronic, systemic, inflammatory autoimmune disease characterized by lymphocyte proliferation and progressive damage to exocrine glands. The diagnosis of SS is challenging due to its complicated clinical manifestations and non-specific signs. Salivary gland biopsy plays an important role in the diagnosis of SS, especially with anti-Sjögren's syndrome antigen A (SSA) and anti-SSB antibody negativity. Histopathology based on biopsy has clinical significance for disease stratification and prognosis evaluation, such as risk assessment for the development of non-Hodgkin's lymphoma. Furthermore, histopathological changes of salivary gland may be implicated in evaluating the efficacy of biological agents in SS. In this review, we summarize the histopathological features of salivary gland, the mechanism of histopathological changes and their clinical significance, as well as non-invasive imaging techniques of salivary glands as a potential alternative to salivary gland biopsy in SS.

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“…SS glandular lesions are due to massive infiltration of inflammatory cells (including T and B lymphocytes, natural killer cells, dendritic cells, and macrophages) and the formation of ectopic germinal centers (8)(9)(10)(11). So far, SS etiology involves poorly elucidated genetic factors.…”

Section: Introductionmentioning

confidence: 99%

Mapping Salivary Proteases in Sjögren’s Syndrome Patients Reveals Overexpression of Dipeptidyl Peptidase-4/CD26

et al. 2021

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Sjögren’s Syndrome (SS) is an autoimmune exocrinopathy characterized by the progressive damage of salivary and lacrimal glands associated with lymphocytic infiltration. Identifying new non-invasive biomarkers for SS diagnosis remains a challenge, and alterations in saliva composition reported in patients turn this fluid into a source of potential biomarkers. Among these, proteases are promising candidates since they are involved in several key physio-pathological processes. This study evaluated differentially expressed proteases in SS individuals’ saliva using synthetic fluorogenic substrates, zymography, ELISA, and proteomic approaches. Here we reported, for the first time, increased activity of the serine protease dipeptidyl peptidase-4/CD26 (DPP4/CD26) in pSS saliva, the expression level of which was corroborated by ELISA assay. Gelatin zymograms showed that metalloproteinase proteolytic band profiles differed significantly in intensity between control and SS groups. Focusing on matrix metalloproteinase-9 (MMP9) expression, an increased tendency in pSS saliva (p = 0.0527) was observed compared to the control group. Samples of control, pSS, and sSS were analyzed by mass spectrometry to reveal a general panorama of proteases in saliva. Forty-eight protein groups of proteases were identified, among which were the serine proteases cathepsin G (CTSG), neutrophil elastase (ELANE), myeloblastin (PRTN3), MMP9 and several protease inhibitors. This work paves the way for proteases to be explored in the future as biomarkers, emphasizing DPP4 by its association in several autoimmune and inflammatory diseases. Besides its proteolytic role, DPP4/CD26 acts as a cell surface receptor, signal transduction mediator, adhesion and costimulatory protein involved in T lymphocytes activation.

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CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

Cited by 43 publications

References 136 publications

Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome

Cytotoxic CD8+ T cells may be drivers of tissue destruction in Sjögren’s syndrome

Recent Advances of Salivary Gland Biopsy in Sjögren's Syndrome

Mapping Salivary Proteases in Sjögren’s Syndrome Patients Reveals Overexpression of Dipeptidyl Peptidase-4/CD26

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