About this Research Topic
Cell death (CD) is crucial for maintaining tissue balance and responding to diseases. In the normal physiological state, cell death is non-immunogenic, and even extensive cell death can trigger regenerative, health-restoring responses or even promoting tumorigenesis. Different forms of CD: chaotic (oncosis-necrotic) and/or regulated (apoptosis, pyropoptosis, necroptosis and ferroptosis) are key elements in hepatic pathological conditions caused by ischemia-reperfusion, viruses, toxins, metabolic issues, or autoimmune factors.
The surge in dying cells results in an overwhelming presence of cell debris and the release of “alarmins”. The turn loose and recognition of these alarmins by specific pattern-recognition receptors in the host resulting in the release pro-inflammatory cytokines. This initiates a cytokine storm, that triggers and worsens giving rise to sterile inflammation, inflicting further damage to the organ which can evolve into liver failure and extrahepatic tissue damage.
Our comprehension of CD pathways as initiators and modulators of disease is continually growing. Many CD pathways can coexist simultaneously in pathological contexts, and several share overlapping mechanisms that can act as a “backup” dying strategy, and the release of various alarmins can elicit diverse reactions in distinct cell types. Understanding how CD pathways operate under different pathological situations remains to be elucidated.
For precise treatment of liver diseases, a combination of distinct inhibitors as well as strategies aimed at blocking the different types of cell death may be necessary to address the multitude of pathways, ultimately enabling the provision of precise and effective treatment options for patients. Nevertheless, dependently of the pathology, the specific inhibition of a type of cell death might be only required. All of this will be addressed in the corresponding Research Topic.
When properly regulated, the innate immune response, initiated by alarmins-sensing, serves as a means of damage control of signaling pathways to recover homeostasis. In contrast, a dysregulated or overt sterile inflammation response can inadvertently lead to further injury. These studies will need to focus on the terminal executioners of CD, as upstream pathway mediators with multiple functions involved in CD and will require development of preclinical models. The various modes of CD and sterile inflammation also represent unique therapeutic avenues for the treatment of human liver diseases. Moreover, cells undergo multiple regulated cell death (RCD) procedures through a wide range of crosstalk that can be activated simultaneously in the context of specific conditions, a fact that is of consistency with the recently proposed concept of PANoptosis (“P,” pyroptosis, “A,” apoptosis; “N,” necroptosis). PANoptosis is a modality of inflammatory RCD mediated by PANoptosome complexes with key features of pyroptosis, apoptosis, and/or necroptosis, which cannot be explained by any of the three RCD mechanisms alone.
In summary, we now recognize several different forms of cell death, executed by different pathways and mediators of sterile inflammation. The mechanisms are being unraveled and their contribution to human liver diseases is being carefully examined. These insights reveal further complexity in hepatic damage, but also provide new and exciting therapeutic opportunities.
In this Research Topic, we welcome the submission of original research, review and mini-review articles with themes including, but not limited to, the following subtopics:
• Characterization of the various forms of CD and their related molecular mechanisms in the context of acute liver diseases, specifically in relation to immunological mechanisms.
• Elucidating the early signs of sterile inflammation and extent of damage from it.
• Establishing new markers of sterile inflammation with the attempt to provide a real time “road map" of the inflammatory component of the disease.
• Provision of precise and effective treatment options targeting immune-inflammatory mechanisms for patients.
Please note: Manuscripts consisting solely of computational analysis of bioinformatics or public genomic or transcriptional databases without validation (independent cohort or in vitro or in vivo biological validation) are outside the scope of this section and are not accepted as part of this research topic. Manuscript dealing with traditional or complementary medicine without a very strong focus on immunological parameters are out of scope for this journal.
The surge in dying cells results in an overwhelming presence of cell debris and the release of “alarmins”. The turn loose and recognition of these alarmins by specific pattern-recognition receptors in the host resulting in the release pro-inflammatory cytokines. This initiates a cytokine storm, that triggers and worsens giving rise to sterile inflammation, inflicting further damage to the organ which can evolve into liver failure and extrahepatic tissue damage.
Our comprehension of CD pathways as initiators and modulators of disease is continually growing. Many CD pathways can coexist simultaneously in pathological contexts, and several share overlapping mechanisms that can act as a “backup” dying strategy, and the release of various alarmins can elicit diverse reactions in distinct cell types. Understanding how CD pathways operate under different pathological situations remains to be elucidated.
For precise treatment of liver diseases, a combination of distinct inhibitors as well as strategies aimed at blocking the different types of cell death may be necessary to address the multitude of pathways, ultimately enabling the provision of precise and effective treatment options for patients. Nevertheless, dependently of the pathology, the specific inhibition of a type of cell death might be only required. All of this will be addressed in the corresponding Research Topic.
When properly regulated, the innate immune response, initiated by alarmins-sensing, serves as a means of damage control of signaling pathways to recover homeostasis. In contrast, a dysregulated or overt sterile inflammation response can inadvertently lead to further injury. These studies will need to focus on the terminal executioners of CD, as upstream pathway mediators with multiple functions involved in CD and will require development of preclinical models. The various modes of CD and sterile inflammation also represent unique therapeutic avenues for the treatment of human liver diseases. Moreover, cells undergo multiple regulated cell death (RCD) procedures through a wide range of crosstalk that can be activated simultaneously in the context of specific conditions, a fact that is of consistency with the recently proposed concept of PANoptosis (“P,” pyroptosis, “A,” apoptosis; “N,” necroptosis). PANoptosis is a modality of inflammatory RCD mediated by PANoptosome complexes with key features of pyroptosis, apoptosis, and/or necroptosis, which cannot be explained by any of the three RCD mechanisms alone.
In summary, we now recognize several different forms of cell death, executed by different pathways and mediators of sterile inflammation. The mechanisms are being unraveled and their contribution to human liver diseases is being carefully examined. These insights reveal further complexity in hepatic damage, but also provide new and exciting therapeutic opportunities.
In this Research Topic, we welcome the submission of original research, review and mini-review articles with themes including, but not limited to, the following subtopics:
• Characterization of the various forms of CD and their related molecular mechanisms in the context of acute liver diseases, specifically in relation to immunological mechanisms.
• Elucidating the early signs of sterile inflammation and extent of damage from it.
• Establishing new markers of sterile inflammation with the attempt to provide a real time “road map" of the inflammatory component of the disease.
• Provision of precise and effective treatment options targeting immune-inflammatory mechanisms for patients.
Please note: Manuscripts consisting solely of computational analysis of bioinformatics or public genomic or transcriptional databases without validation (independent cohort or in vitro or in vivo biological validation) are outside the scope of this section and are not accepted as part of this research topic. Manuscript dealing with traditional or complementary medicine without a very strong focus on immunological parameters are out of scope for this journal.
Keywords: Acute Liver Diseases, Cell Death, Cell Death Mechanisms, CD, Alarmins, DAMPs, Sterile Inflammation, Biomarkers, experimental models, therapeutic strategies
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.
