Research Topic

Physiological Roles of Inflammasomes

About this Research Topic

Inflammasomes are cytoplasmic multi-protein complexes whose formation are ligand dependent and include cysteine proteases such as caspase-1. Upon activation, these cysteine proteases cleave themselves and immature IL-1 type cytokines, such as pro-IL-1β and pro-IL-18, leading to cellular release and activation of their biological functions. Prototypical inflammasomes are composed of either an indirect or direct signal - such as an immune stimulatory pathogen or a danger associated molecular pattern (P/DAMP) sensor such as NLR family pyrin domain containing protein (NLRP) 3 or absent in melanoma (AIM) 2, respectively. Beyond the processing of IL-1 type cytokine towards maturation, inflammasome activity also triggers inflammation- associated cell death, namely pyroptosis. Non-canonical inflammasomes containing caspase-8 or caspase-11/4/5 have also been identified as executors in mediating IL-1β/IL-18 release or pyroptosis.

Human genetic studies as well as related research on animal models have indicated that the deregulation of inflammasomes is a causative factor of numerous pathologies, including those driving specific autoimmune such as acutely autoinflammatory and metabolic diseases, as well as cancer. From the point of view of evolution, however, the fact that inflammasomes have been conserved in many species argues that they should be more beneficial than deleterious. Accumulating evidence has shown that as a critical effector mechanism of host innate immunity, concerted inflammasome activation drives important immune responses to xenobiotic or traumatic insults. Experimental mice deficient for the components of inflammasomes such as caspase-1, ASC, NLRP3 or AIM2 have all been demonstrated to be defective in defending infectious challenges from multiple microbes. This is due, at least in part, to insufficient inflammatory responses mounted in such animals. However, in comparison with research into the pathological effects of the inflammasome, the positive role of inflammasomes in host immune defenses remains poorly understood.

Working as a “double edged sword”, inflammasome functions need to be tightly regulated in order to fulfil normal physiological roles while simultaneously preventing pathological damage to the host. Our increased understanding of the mechanisms involved in these processes is essential for the clinical translation of inflammasome research.

In this Research Topic, we aim to focus on characterizing the beneficial functions of the inflammasome within the immune system with the aim of accelerating the development of novel strategies for therapeutic interventions concerning inflammasome modulation. Accordingly, we welcome the submission of Original Research, Review and Mini-Review articles on the physiological function of inflammasomes, as well as on the transition from physiological to pathological inflammasome function in experimental models of diseases. Studies on the mechanisms for the activation or regulation of inflammasomes in various species are also welcome.


Keywords: Inflammasome


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Inflammasomes are cytoplasmic multi-protein complexes whose formation are ligand dependent and include cysteine proteases such as caspase-1. Upon activation, these cysteine proteases cleave themselves and immature IL-1 type cytokines, such as pro-IL-1β and pro-IL-18, leading to cellular release and activation of their biological functions. Prototypical inflammasomes are composed of either an indirect or direct signal - such as an immune stimulatory pathogen or a danger associated molecular pattern (P/DAMP) sensor such as NLR family pyrin domain containing protein (NLRP) 3 or absent in melanoma (AIM) 2, respectively. Beyond the processing of IL-1 type cytokine towards maturation, inflammasome activity also triggers inflammation- associated cell death, namely pyroptosis. Non-canonical inflammasomes containing caspase-8 or caspase-11/4/5 have also been identified as executors in mediating IL-1β/IL-18 release or pyroptosis.

Human genetic studies as well as related research on animal models have indicated that the deregulation of inflammasomes is a causative factor of numerous pathologies, including those driving specific autoimmune such as acutely autoinflammatory and metabolic diseases, as well as cancer. From the point of view of evolution, however, the fact that inflammasomes have been conserved in many species argues that they should be more beneficial than deleterious. Accumulating evidence has shown that as a critical effector mechanism of host innate immunity, concerted inflammasome activation drives important immune responses to xenobiotic or traumatic insults. Experimental mice deficient for the components of inflammasomes such as caspase-1, ASC, NLRP3 or AIM2 have all been demonstrated to be defective in defending infectious challenges from multiple microbes. This is due, at least in part, to insufficient inflammatory responses mounted in such animals. However, in comparison with research into the pathological effects of the inflammasome, the positive role of inflammasomes in host immune defenses remains poorly understood.

Working as a “double edged sword”, inflammasome functions need to be tightly regulated in order to fulfil normal physiological roles while simultaneously preventing pathological damage to the host. Our increased understanding of the mechanisms involved in these processes is essential for the clinical translation of inflammasome research.

In this Research Topic, we aim to focus on characterizing the beneficial functions of the inflammasome within the immune system with the aim of accelerating the development of novel strategies for therapeutic interventions concerning inflammasome modulation. Accordingly, we welcome the submission of Original Research, Review and Mini-Review articles on the physiological function of inflammasomes, as well as on the transition from physiological to pathological inflammasome function in experimental models of diseases. Studies on the mechanisms for the activation or regulation of inflammasomes in various species are also welcome.


Keywords: Inflammasome


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 March 2018 Abstract
30 June 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 March 2018 Abstract
30 June 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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