Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis

Zhou, Jiannan; Pathak, Janak L.; Wu, Lihong; Chen, Bo; Cao, Tingting; Wei, Wei; Wu, Xiaodan; Chen, Guiping; Watanabe, Nobumoto; Li, Xiaomeng; Li, Jiang

doi:10.1016/j.freeradbiomed.2024.04.003

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…An increase in the number of CD39+ CD8+ T cells found in Crohn’s patients is correlated with enhanced signal transduction of reactive oxygen species (ROS) ( 16 ). The ROS/pSTAT4/important protein aquaporin 5 axis affects salivary dysfunction in SS ( 18 ). Although some studies have focused on Tregs and SS, the role of Tregs in the occurrence and development of SS remains elusive.…”

Section: Discussionmentioning

confidence: 99%

The causal relationship between immune cells and Sjögren’s syndrome: a univariate, multivariate, bidirectional Mendelian randomized study

Zeng,

Huang,

Zeng

et al. 2024

Front. Med.

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IntroductionImmune cells are involved in the onset and progression of Sjögren’s syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated.MethodsWe conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS.ResultsAfter false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS.ConclusionThese findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.

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Section: Discussionmentioning

confidence: 99%

The causal relationship between immune cells and Sjögren’s syndrome: a univariate, multivariate, bidirectional Mendelian randomized study

Zeng,

Huang,

Zeng

et al. 2024

Front. Med.

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The role of cytokines from salivary gland epithelial cells in the immunopathology of Sjögren’s syndrome

Dong,

Wang,

2024

Front. Immunol.

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In the pathogenesis and progression of Sjögren’s syndrome (SS), hematopoietic cells in the peripheral circulation, tissue-resident immune cells, and parenchymal cells of salivary gland tissues (such as epithelial cells, endothelial cells, fibroblasts, etc.) all play crucial roles. These diverse cells form intricate networks and interact with each other, leading to tissue destruction and persistent chronic inflammation, ultimately causing irreversible damage in glandular function. Among these, salivary gland epithelial cells (SGECs) consistently hold a key position, characterized by their functions in expressing co-stimulatory and antigen-presenting molecules and secreting pro-inflammatory cytokines and chemokines. Moreover, SGECs actively engage in and facilitate the development of specific pathological structures within the salivary gland, such as lymphoepithelial lesions (LELs) and tertiary lymphoid structures (TLSs), thereby substantially elevating the risk of mucosa-associated lymphoid tissue (MALT) lymphoma. Overall, SGECs are recognized for their essential and irreplaceable contributions to the pathogenesis of SS. This review article initially delves into the anatomical composition of salivary gland epithelial cells, subsequently focusing on elucidating the different cytokines derived from SGECs, encompassing chemokines, pro-inflammatory cytokines, anti-inflammatory cytokines, pro-survival cytokines, and damage-associated molecular patterns (DAMPs), to explore their key roles in the pathogenesis of SS.

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Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis

Cited by 2 publications

References 27 publications

The causal relationship between immune cells and Sjögren’s syndrome: a univariate, multivariate, bidirectional Mendelian randomized study

The causal relationship between immune cells and Sjögren’s syndrome: a univariate, multivariate, bidirectional Mendelian randomized study

The role of cytokines from salivary gland epithelial cells in the immunopathology of Sjögren’s syndrome

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