Immune checkpoint molecule Tim-3 promotes NKT cell apoptosis and predicts poorer prognosis in Sepsis

Wu, Han; Tang, Ting-Xuan; Deng, Hai; Deng, Chao; Zhang, Chong; Luo, Jialiu; Chen, Shunyao; Zhang, Peidong; Yang, Jing‐Zhi; Dong, Liming; Chang, Teding; Tang, Zhaohui

doi:10.1016/j.clim.2023.109249

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…TIM-3 expression on NK cells has been associated with functional impairment and diminished cytotoxic activity. The engagement of TIM-3 on NK cells by its ligands may contribute to the regulation of NK cell function and impact overall immune responses ( 13 ). These observations suggest that TIM-3 serves as a vital modulator of immune responses across various cell types, contributing significantly to immune homeostasis and preventing excessive immunopathology ( 29 ).…”

Section: Tim-3: An Overviewmentioning

confidence: 99%

“…Wu et al. discovered a close correlation between the expression of TIM-3 and the functional status of NKT cells in septic patients ( 13 ). They found that upregulated TIM-3 expression promoted NKT cell activation and apoptosis during early sepsis, leading to worse disease severity and prognosis.…”

Section: The Role Of Tim-3 In Sepsismentioning

confidence: 99%

“…To investigate the potential of targeting TIM-3 as an immunomodulatory strategy for sepsis management, they blocked the TIM-3/Galectin-9 signal axis using α-lactose in a mouse model of CLP. This inhibition of NKT cell apoptosis protected against septic challenge, indicating the potential of targeting TIM-3 in sepsis ( 13 ). Similarly, Yao et al.…”

Section: The Role Of Tim-3 In Sepsismentioning

confidence: 99%

“…Initially identified on T cells, TIM-3 is now known to be expressed on multiple immune cell types, including natural killer cells, dendritic cells, and macrophages (8)(9)(10). Altered expression and dysregulation of TIM-3 have been observed in sepsis patients, hinting at its involvement in the pathogenesis of this condition (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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The role of TIM-3 in sepsis: a promising target for immunotherapy?

Wang,

Liu,

et al. 2024

Front. Immunol.

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Sepsis remains a significant cause of mortality and morbidity worldwide, with limited effective treatment options. The T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) has emerged as a potential therapeutic target in various immune-related disorders. This narrative review aims to explore the role of TIM-3 in sepsis and evaluate its potential as a promising target for immunotherapy. We discuss the dynamic expression patterns of TIM-3 during sepsis and its involvement in regulating immune responses. Furthermore, we examine the preclinical studies investigating the regulation of TIM-3 signaling pathways in septic models, highlighting the potential therapeutic benefits and challenges associated with targeting TIM-3. Overall, this review emphasizes the importance of TIM-3 in sepsis pathogenesis and underscores the promising prospects of TIM-3-based immunotherapy as a potential strategy to combat this life-threatening condition.

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Section: Tim-3: An Overviewmentioning

confidence: 99%

Section: The Role Of Tim-3 In Sepsismentioning

confidence: 99%

Section: The Role Of Tim-3 In Sepsismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of TIM-3 in sepsis: a promising target for immunotherapy?

Wang,

Liu,

et al. 2024

Front. Immunol.

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“…The detection of biomarkers promises to offer improved opportunities for disease diagnosis, prognosis, and prevention ( 14 ). Therefore, focusing on the role of ER-related genes (ERRGs) in sepsis is becoming crucial in fully understanding the diagnosis, evaluation, and treatment of sepsis.…”

Section: Introductionmentioning

confidence: 99%

The development of endoplasmic reticulum-related gene signatures and the immune infiltration analysis of sepsis

Zhou

Chen

et al. 2023

Front. Immunol.

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BackgroundSepsis is a complex condition involving multiorgan failure, resulting from the hosts’ deleterious systemic immune response to infection. It is characterized by high mortality, with limited effective detection and treatment options. Dysregulated endoplasmic reticulum (ER) stress is directly involved in the pathophysiology of immune-mediated diseases.MethodsClinical samples were obtained from Gene Expression Omnibus datasets (i.e., GSE65682, GSE54514, and GSE95233) to perform the differential analysis in this study. A weighted gene co-expression network analysis algorithm combining multiple machine learning algorithms was used to identify the diagnostic biomarkers for sepsis. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and the single-sample gene set enrichment analysis algorithm were used to analyze immune infiltration characteristics in sepsis. PCR analysis and western blotting were used to demonstrate the potential role of TXN in sepsis.ResultsFour ERRGs, namely SET, LPIN1, TXN, and CD74, have been identified as characteristic diagnostic biomarkers for sepsis. Immune infiltration has been repeatedly proved to play a vital role both in sepsis and ER. Subsequently, the immune infiltration characteristics result indicated that the development of sepsis is mediated by immune-related function, as four diagnostic biomarkers were strongly associated with the immune infiltration landscape of sepsis. The biological experiments in vitro and vivo demonstrate TXN is emerging as crucial player in maintaining ER homeostasis in sepsis.ConclusionOur research identified novel potential biomarkers for sepsis diagnosis, which point toward a potential strategy for the diagnosis and treatment of sepsis.

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