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Inflammatory processes in the liver: divergent roles in homeostasis and pathology

Abstract

The hepatic immune system is designed to tolerate diverse harmless foreign moieties to maintain homeostasis in the healthy liver. Constant priming and regulation ensure that appropriate immune activation occurs when challenged by pathogens and tissue damage. Failure to accurately discriminate, regulate, or effectively resolve inflammation offsets this balance, jeopardizing overall tissue health resulting from an either  overly tolerant or an overactive inflammatory response. Compelling scientific and clinical evidence links dysregulated hepatic immune and inflammatory responses upon sterile injury to several pathological conditions in the liver, particularly nonalcoholic steatohepatitis and ischemia-reperfusion injury. Murine and human studies have described interactions between diverse immune repertoires and nonhematopoietic cell populations in both physiological and pathological activities in the liver, although the molecular mechanisms driving these associations are not clearly understood. Here, we review the dynamic roles of inflammatory mediators in responses to sterile injury in the context of homeostasis and disease, the clinical implications of dysregulated hepatic immune activity and therapeutic developments to regulate liver-specific immunity.

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Funding

This research was supported by an SFI Frontiers Grant.

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O.A. drafted the manuscript, designed the figures, and contributed to the main conceptual ideas. M. W. R. contributed to the writing, provided critical feedback, and helped shape the manuscript. C.O.F. designed and directed the review, supervised the work, and contributed to the writing of the manuscript.

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Correspondence to Cliona O’Farrelly.

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The authors declare no competing interests.

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Ahmed, O., Robinson, M.W. & O’Farrelly, C. Inflammatory processes in the liver: divergent roles in homeostasis and pathology. Cell Mol Immunol 18, 1375–1386 (2021). https://doi.org/10.1038/s41423-021-00639-2

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Keywords

  • homeostasis
  • immunology
  • inflammation
  • liver

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