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World J Hepatol. Jan 27, 2023; 15(1): 52-67
Published online Jan 27, 2023. doi: 10.4254/wjh.v15.i1.52
Liver immunity, autoimmunity, and inborn errors of immunity
Yavuz Emre Parlar, Sefika Nur Ayar, Deniz Cagdas, Yasemin H Balaban
Yavuz Emre Parlar, Yasemin H Balaban, Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
Sefika Nur Ayar, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
Deniz Cagdas, Department of Pediatric Immunology, Hacettepe University Ihsan Dogramaci Children's Hospital, Ankara 06100, Turkey
Author contributions: Parlar YE and Balaban YH contributed equally in collecting the data and writing the paper; Ayar SN and Cagdas D edited the manuscript and contributed opinions on liver immunity; all authors have read and approved the final manuscript.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yavuz Emre Parlar, MD, Research Fellow, Department of Gastroenterology, Hacettepe University Faculty of Medicine, Hacettepe University Sihhiye Campus, 06100 Sihhiye/Ankara, Ankara 06100, Turkey. yavuzemreparlar@gmail.com
Received: September 17, 2022
Peer-review started: September 17, 2022
First decision: October 22, 2022
Revised: October 23, 2022
Accepted: December 23, 2022
Article in press: December 23, 2022
Published online: January 27, 2023
Processing time: 120 Days and 14.2 Hours
Abstract

The liver is the front line organ of the immune system. The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens. This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens, such as food antigens or pathogens. As an immune active organ, the liver functions as a gatekeeping barrier from the outside world, and it can create a rapid and strong immune response, under unfavorable conditions. However, the liver's assumed immune status is anti-inflammatory or immuno-tolerant. Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance. The anatomical structure of the liver can facilitate the preparation of lymphocytes, modulate the immune response against hepatotropic pathogens, and contribute to some of its unique immunological properties, particularly its capacity to induce antigen-specific tolerance. Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane, circulating lymphocytes can closely contact with antigens, displayed by endothelial cells, Kupffer cells, and dendritic cells while passing through the sinusoids. Loss of immune tolerance, leading to an autoaggressive immune response in the liver, if not controlled, can lead to the induction of autoimmune or autoinflammatory diseases. This review mentions the unique features of liver immunity, and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.

Keywords: Liver immunity; Autoimmunity; Immune tolerance; Autoinflamation; Autoimmune liver diseases; Inborn errors of immunity

Core Tip: The various repertoires of immune cell populations in the liver play a central role in maintaining homeostasis between inflammation and tolerance. Inflammatory and immunoregulatory interactions within the liver are essential for maintaining systemic homeostasis. In this review, we summarize the molecular mechanisms involved in these seemingly contradictory immune processes and how liver immunity functions during normal liver homeostasis and liver pathologies, such as viral hepatitis, autoimmune hepatitis, and hepatocellular cancer.