TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury

Lan, Peixiang; Fan, Yihui; Zhao, Yue; Lou, Xudong; Monsour, Howard Paul; Zhang, Xiaolong; Choi, Yongwon; Yu, Dou; Ishii, Naoto; Ghobrial, Rafik M.; Xiao, Xiang; Li, Xian Chang

doi:10.1172/jci91075

Cited by 46 publications

(50 citation statements)

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“…49 In the AH patient livers, functional macrophages are often depleted and pyroptosis may be involved in such condition which further aggravate neutrophilic infiltration to fight against bacteria. Eosinophils 52 and invariant natural killer T cells 53 are also shown to undergo pyroptosis in response to liver injury. Future studies have to address how pyroptosis of parenchymal and non-parenchymal liver cells determines the pathologic outcome in the disease-specific setting.…”

Section: Pyroptosismentioning

confidence: 99%

Cell Death and Liver Disease

2020

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Cell death is now reclassified into several types based on the mechanisms and morphologic phenotype. Understanding of such classifications offers insights into the pathogenesis of liver disease, as well as diagnostic or therapeutic implications. Apoptosis is recognized relatively easily due to its unique morphology, but lytic cell death may occur in the form of accidental necrosis, mitochondria permeability transitiondriven necrosis, necroptosis, pyroptosis, ferroptosis, and parthanatos. The cell may be engulfed by neighboring cells due to a loss of integrin signaling or cancer cell competition by entosis, a type of cell death. The classification also includes mechanistically termed cell death such as autophagy-dependent cell death and lysosome-dependent cell death. These different types of cell death may occur uniquely in certain liver diseases but may coexist in the evolution of the disease. They occur in parenchymal and non-parenchymal liver cells, as well as inflammatory cells, causing distinct pathologic consequences. This review briefly covers the recently revised classifications of cell death and discusses their relevance to liver diseases of different etiologies.

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Section: Pyroptosismentioning

confidence: 99%

Cell Death and Liver Disease

2020

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“…These are mostly found in hepatic sinusoids and are able to activate hepatic stellate cells, as well as to mediate hepatocytes' killing [246]. Liver iNKT cells constitutively express OX40, which is involved in inducing proinflammatory and profibrotic liver injury, as reported by Lan and colleagues [247]. Although iNKT role in autoimmune liver disease is still not fully understood, it has been reported that these activated cells mediate a major role in inflammation and hepatocyte death in a murine model of Con-A-induced autoimmune hepatitis [248].…”

Section: Vitamin D and Autoimmune Liver Diseasesmentioning

confidence: 74%

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

et al. 2020

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Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

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“…OX40 (CD134) is widely considered a T cell costimulatory molecule that is time-dependently expressed in activated CD4 + T cells and CD8 + T cells (10). OX40 is essential for the T cell regulation of cell proliferation, survival, differentiation, and even cytokine production (11), which are associated with inflammatory immune activation in many liver diseases, such as hepatitis B (12), hepatocellular carcinoma (13), and concanavalin A-induced hepatitis (14). Interestingly, by performing an in vitro stimulation and analysis of neutrophils from healthy human PBMCs, one group reported that OX40 is constitutively expressed in human peripheral blood neutrophils and regulates neutrophil survival, indicating that OX40 contributes not only to adaptive immunity but also to innate immunity (15).…”

Section: Introductionmentioning

confidence: 99%