Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-κB signaling pathway in CD4 T cells

Huang, Siyuan; Liu, Di; Sun, Jianhui; Zhang, Huacai; Zhang, Jing; Wang, Qiang; Gan, Lebin; Qu, Guoxin; Qiu, Jinchao; Deng, Jin; Jiang, Jianxin

doi:10.1016/j.ymthe.2021.12.013

Cited by 40 publications

(32 citation statements)

References 42 publications

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“…Paired-end sequence files (fastq) were aligned to hg38 using Hisat2 (Hierarchical Indexing for Spliced Alignment of Transcripts, version 2.0.5) as described previously. 30 The output SAM (sequencing alignment/map) files were converted to BAM (binary alignment/map) files and sorted using SAMtools (version 1.3.1). Gene abundance was expressed as fragments per kilobase of exon per million reads mapped (FPKM).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Bao¹,

Ye²,

Xu³

et al. 2022

Molecular Therapy - Nucleic Acids

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Section: Methodsmentioning

confidence: 99%

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Bao¹,

Ye²,

Xu³

et al. 2022

Molecular Therapy - Nucleic Acids

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“…In addition to the PD-1 and PD-L1 axes, TIM-3 expression is significantly increased on CD4 + T cells in patients with sepsis. Conditional knockout of TIM-3 in CD4 + T cells protects infectiously immunosuppressed mice from death by reducing organ dysfunction [ 100 ]. CTLA-4 transmits inhibitory signals to T cells and inhibits their activation by binding to CD80 and CD86.…”

Section: Mechanism Of Sepsis-induced Immunosuppressionmentioning

confidence: 99%

“…Therapies targeting negative costimulatory molecules increase host resistance to infection and improve outcomes. A preclinical study shows that conditional knockout of TIM-3 in CD4 + T cells or systemic knockout of TIM-3 reduces immunosuppression-related mortality in a mouse model of sepsis [ 100 ]. Another study investigated the ability to block PD-1 to restore innate and acquired immune cell function [ 169 ].…”

Section: Activating Immunities To Fight Sepsismentioning

confidence: 99%

Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options

et al. 2022

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Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

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“…For example, Huang et al. observed that the expression of TIM-3 on CD4 T cells in patients with sepsis-induced immunosuppression was significantly elevated, which impaired anti-infective responses and positively correlated with mortality ( 51 ). Hou et al.…”

Section: The Immunological Characteristics Of Sepsismentioning

confidence: 99%

Natural killer cells in sepsis: Friends or foes?

Wang

Cui

et al. 2023

Front. Immunol.

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Sepsis is one of the major causes of death in the hospital worldwide. The pathology of sepsis is tightly associated with dysregulation of innate immune responses. The contribution of macrophages, neutrophils, and dendritic cells to sepsis is well documented, whereas the role of natural killer (NK) cells, which are critical innate lymphoid lineage cells, remains unclear. In some studies, the activation of NK cells has been reported as a risk factor leading to severe organ damage or death. In sharp contrast, some other studies revealed that triggering NK cell activity contributes to alleviating sepsis. In all, although there are several reports on NK cells in sepsis, whether they exert detrimental or protective effects remains unclear. Here, we will review the available experimental and clinical studies about the opposing roles of NK cells in sepsis, and we will discuss the prospects for NK cell-based immunotherapeutic strategies for sepsis.

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Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-κB signaling pathway in CD4 T cells

Cited by 40 publications

References 42 publications

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV

Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options

Natural killer cells in sepsis: Friends or foes?

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