Negative regulation of Nod‐like receptor protein 3 inflammasome activation by T cell Ig mucin‐3 protects against peritonitis

Wang, Wei; Shi, Qingzhu; Dou, Shuaijie; Li, Ge; Shi, Xinhui; Jiang, Xingwei; Wang, Zhiding; Yu, Dandan; Chen, Guojiang; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jie; Shen, Beifen; Ma, Yuanfang; Han, Gencheng

doi:10.1111/imm.12812

Cited by 24 publications

(17 citation statements)

References 41 publications

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“…showed in peritoneal macrophages that LIPIN‐2 negatively regulates ATP‐induced opening of P2X7 receptor channel to inhibit K + efflux. More recently, transmembrane immunoglobulin and mucin domain (TIM)‐3, a molecule involved in negative regulation of T cell activation and phagocytosis in macrophages, was demonstrated to negatively regulate LPS+ATP‐induced NLRP3 inflammasome activation in murine peritoneal and J774 macrophages . Blocking TIM‐3‐signaling with soluble TIM‐3 Ig protein for 1 h in J774 macrophages reduced intracellular K + levels suggesting an inhibitory role for TIM‐3 in K + efflux .…”

Section: Negative Regulation Of Nlrp3 Inflammasome Activationmentioning

confidence: 99%

An update on cell intrinsic negative regulators of the NLRP3 inflammasome

Poudel

Gurung

2018

Journal of Leukocyte Biology

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Inflammasomes are multimeric protein complexes that promote inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. The central role of inflammasomes in combating infection and maintaining homeostasis has been studied extensively. Although inflammasome-mediated inflammation and cell death are vital to limit pathogenic insults and to promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation, and cell death can cause cytokine storm, tissue damage, autoinflammatory and autoimmune diseases, and even death in the afflicted individuals. NLRP3 is one of the major cytosolic sensors that assemble an inflammasome. Given the adverse consequences of uncontrolled inflammasome activation, our immune system has developed tiered mechanisms to inhibit NLRP3 inflammasome activation. In this review, we highlight and discuss recent advances and our current understanding of mechanisms by which NLRP3 inflammasome can be negatively regulated.

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Section: Negative Regulation Of Nlrp3 Inflammasome Activationmentioning

confidence: 99%

An update on cell intrinsic negative regulators of the NLRP3 inflammasome

Poudel

Gurung

2018

Journal of Leukocyte Biology

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“…Само развитие РГП определяет наличие нарушений в регуляторных и эффекторных механизмах местного и системного иммунитета [7,30]. Кроме того, хирургическое вмешательство 19,1 (14,1) 19,3 (16,9) 33,5 (31,2-35,8) p 1 = 0,032 p 1,2 < 0,001 p 4 = 0,012 Примечание.…”

Section: Discussionunclassified

“…Доказано, что само течение инфекционного процесса в брюшной полости, характер и особенности развития гнойных послеоперацион-ных осложнений определяются не только тяжестью основного заболевания, адекватностью выполненного оперативного вмешательства и полнотой проводимой интенсивной терапии, но и функциональным состоянием иммунной системы [1,10,30]. Установлено, что повышение функциональной активности В-лимфоцитов приводит к затруднению развития антигензависимого перитонита у мышей в эксперименте [25].…”

Section: Introductionunclassified

Peculiarities of the phenotype of T-lymphocytes in the dynamics of the postoperating period in patients with peritonite depending on the outcome of disease

Савченко

Борисов

Черданцев

et al. 2019

Russian Journal of Infection and Immunity

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The aim of the study was to investigate the phenotype of blood T-lymphocytes in the dynamics of the postoperative period in patients with widespread purulent peritonitis (WPP) depending on the outcome of the disease. A total of 36 patients aged 30-65 with acute surgical diseases and abdominal injuries complicated by WPP years were examined. Blood sampling was performed before the operation (preoperative period), and also on the 7 th , 14 th and 21 st day of the postoperative period. 40 relatively healthy people of the same age range were examined as a control. Study of the phenotype of blood Tlymphocytes was carried out by the method of 5-color flow cytometry using direct immunofluorescence of whole periphe ral blood. Mean levels of fluorescence were used to evaluate the expression levels of surface receptors. It was established that in the preoperative period in patients with WPP regardless of the outcome of the disease against the background of a decrease in the absolute amount of total lymphocytes in the blood the content of T cells increases. The T-lymphocytes of patients with WPP are significantly more intense expressing the CD28 and CD62L receptors than the cells of healthy people. In the preoperative period and within two weeks of postoperative treatment with a favorable outcome of the WPP an increased amount of CD62L + T-lymphocytes is detected in comparison with the indices of patients with an unfavorable outcome of the disease. Other features of the phenotypic composition of T-lymphocytes in patients with a favorable outcome of WPP is an increase in T-regulatory activity which manifests itself both in the preoperative period and within two weeks of postoperative treatment. With a favorable outcome of WPP an increase in the number of activated cytotoxic T-lymphocytes is observed on the 14th day of treatment which with an unfavorable outcome is observed only on the 21 st day of treatment. It is assumed that T-cell suppression and activation of cytotoxic T cells are the factors determining a decrease in the intensity of inflammatory processes in WPP and thereby increasing the level of the favorable outcome of the disease. In case of an unfavorable outcome of the disease, postoperative therapy has a weaker or delayed effect on the dynamics of the studied parameters than with a favorable outcome. With a favorable outcome of WPP an increase in the CD3 + CD57 + cell count is observed already from the second week of treatment and is more pronounced whereas in the case of an adverse outcome of WPP an increase in the level of these cells is observed only at the third week of treatment. However, the level of expression of CD57 on T-lymphocytes is more pronounced throughout the course of the examination with an unfavorable outcome of WPP.

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“…Tim-3 is expressed on macrophages and, in various disease models, has been associated with inhibitory function 34 . More recently, Tim-3 has been shown to act as a negative regulator of the NLRP3 inflammasome by dampening NF-κB responses in mouse peritoneal macrophages 35 . The authors further showed that tyrosines 256 and 263 near the Tim-3 C-terminus are necessary for NLRP3 inhibition by Tim-3 and, in a model of peritonitis blockade of Tim-3, led to increased pathology.…”

Section: Tim-3 and Innate Immunitymentioning

confidence: 99%

Immune regulation by Tim-3

Banerjee

Kane

2018

F1000Res

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T-cell immunoglobulin and mucin domain 3 (Tim-3) is a transmembrane protein that in both mice and humans has been shown to possess various functions in a context-dependent manner. Thus, Tim-3 has been associated with both inhibitory and co-stimulatory function, depending in part on the specific cell type and immune response course. Though originally described on T cells, Tim-3 is now known to be expressed by both lymphoid and non-lymphoid cells within the immune system and even by non-immune cells. In addition, though widely thought of as a negative regulator of immunity, Tim-3 has been shown in more recent studies to have a positive function on both myeloid and lymphoid cells, including T cells. Tim-3 is often expressed at a high level on exhausted T cells in tumors and chronic infection and may engage in crosstalk with other so-called “checkpoint” molecules such as PD-1. Thus, Tim-3 has emerged as a possible therapeutic target, which is being actively explored both pre-clinically and clinically. However, recent research suggests a more complex in vivo role for this protein, compared with other targets in this area.

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Negative regulation of Nod‐like receptor protein 3 inflammasome activation by T cell Ig mucin‐3 protects against peritonitis

Cited by 24 publications

References 41 publications

An update on cell intrinsic negative regulators of the NLRP3 inflammasome

An update on cell intrinsic negative regulators of the NLRP3 inflammasome

Peculiarities of the phenotype of T-lymphocytes in the dynamics of the postoperating period in patients with peritonite depending on the outcome of disease

Immune regulation by Tim-3

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