Innate Immune Cell Trafficking and Function During Sterile Inflammation of the Liver
Abstract
The sterile inflammatory response (inflammation in the absence of infection) to tissue injury and cell death is required for normal wound healing. However, dysregulated sterile inflammation leads to various acute and chronic inflammatory diseases, including those of the liver and gastrointestinal tract. It is therefore important to increase our understanding of the mechanisms that control physiological versus pathological sterile inflammation. We have begun to clarify the cellular and molecular mechanisms that coordinate the innate immune response to tissue damage and cell death in the liver. In this review, we summarize the mechanisms that alert the immune system to the presence of tissue damage and highlight recent advances in our understanding of innate immune cell trafficking to sites of hepatic sterile inflammation. We explore the functions of various innate immune cells in the coordination of tissue repair, including previously underappreciated roles of peritoneal macrophages and platelets. We propose that dysregulation of immune cell trafficking or function at sites of tissue injury contributes to the misdirection of sterile inflammation to promote chronic inflammatory disease.
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DAMPs released from damaged hepatocytes initiate or amplify inflammatory responses in sterile liver injury, analogous to pathogen-associated molecular patterns.
“Indeed, the role of DAMPs released from damaged hepatocytes in initiating or amplifying an inflammatory response, analogous to pathogen-associated molecular patterns of infectious pathogens in sterile liver injury, is now well recognized28.”
From Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis (2020) · cites this paper as [28]
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- Authors
- McDonald, B., & Kubes, P.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Kubes, Paul
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 151
- Issue
- 6
- Pages
- 1087-1095
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2531302392
- Cited by
- 123
- References
- 63
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 11 · 2023: 10 · 2022: 20 · 2021: 19 · 2020: 13 · 2019: 16 · 2018: 16 · 2017: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- sterile inflammation, innate immunity, immune cell trafficking, liver, tissue damage, cell death, peritoneal macrophages, platelets, tissue repair, wound healing, chronic inflammatory diseases
- MeSH terms
- Animals, Blood Platelets, Chemotaxis, Hepatitis, Humans, Immunity, Innate, Macrophages, Monocytes, Neutrophils, Cell Death
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