Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 2:14:1175147.
doi: 10.3389/fimmu.2023.1175147. eCollection 2023.

Innate immunity and early liver inflammation

Jordi Yang Zhou  1   2
Affiliations
Review

Innate immunity and early liver inflammation

Jordi Yang Zhou. Front Immunol. .

Abstract

The innate system constitutes a first-line defence mechanism against pathogens. 80% of the blood supply entering the human liver arrives from the splanchnic circulation through the portal vein, so it is constantly exposed to immunologically active substances and pathogens from the gastrointestinal tract. Rapid neutralization of pathogens and toxins is an essential function of the liver, but so too is avoidance of harmful and unnecessary immune reactions. This delicate balance of reactivity and tolerance is orchestrated by a diverse repertoire of hepatic immune cells. In particular, the human liver is enriched in many innate immune cell subsets, including Kupffer cells (KCs), innate lymphoid cells (ILCs) like Natural Killer (NK) cells and ILC-like unconventional T cells - namely Natural Killer T cells (NKT), γδ T cells and Mucosal-associated Invariant T cells (MAIT). These cells reside in the liver in a memory-effector state, so they respond quickly to trigger appropriate responses. The contribution of aberrant innate immunity to inflammatory liver diseases is now being better understood. In particular, we are beginning to understand how specific innate immune subsets trigger chronic liver inflammation, which ultimately results in hepatic fibrosis. In this review, we consider the roles of specific innate immune cell subsets in early inflammation in human liver disease.

Keywords: Gd T cell; Hepatitis (general); Inflammation; Innate immnuity; MAIT cell; NK cells; NKT (natural killer T) cell; kupffer cell (KC).

PubMed Disclaimer

Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Diagrammatic representation of the liver architecture. The classical hexagonal lobule constitutes the anatomic unit of the liver. The lobule´s parenchyma is mainly formed by hepatocytes that are distributed along the sinusoids. The portal triad, formed by the hepatic artery (HA), the portal vein (PV) and the biliary duct (BD), carries the blood supply towards the centroid of the lobule where it is collected by the central vein (CV). Within the sinusoids, Kupffer cells (K) and Natural Killer cells (NK) are located in close proximity to the endothelium (beige). Other ILC-like cells such as iNKT cells and T2NKT cells are constantly surveying the sinusoids. Closer to the triad, especially near the BDs, there is a high frequency of MAIT cells and γδ T cells.
Figure 2
Figure 2
(A) Diagram tree of the approximate frequency of liver-resident cells and a FACS-based gating strategy to identify each cell type. The liver is mainly constituted by parenchyma (hepatocytes) and ILCs. Among ILCs, Kupffer cells and NK cells are the most abundant immune cells. The liver is also characteristic for having a niche of unconventional T cells, namely iNKT cells, T2NKT cells, γδ T cells and MAIT cells. (B) The main types of antigen recognition by unconventional T cells through their T-cell receptors (TCRs), Kupffer cells and NK cells. Kupffer cells and NK cells are activated through pattern recognition receptors. Additionally, NK cells have receptors that can sense healthy and stressed or dead cells.
Figure 3
Figure 3
Hepatitis is a hallmark of the majority of liver diseases.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Wisse E, Braet F, Luo D, deZanger R, Jans D, Crabbé E, et al. . Structure and function of sinusoidal lining cells in the liver. Toxicol Pathol (1996) 24:100–11. doi: 10.1177/019262339602400114 - DOI - PubMed
    1. Wake K, Sato T. “The sinusoid” in the liver: lessons learned from the original definition by Charles Sedgwick Minot (1900). Anat Rec (Hoboken) (2015) 298:2071–80. doi: 10.1002/ar.23263 - DOI - PubMed
    1. Ben-Moshe S, Itzkovitz S. Spatial heterogeneity in the mammalian liver. Nat Rev Gastroenterol Hepatol (2019) 16:395–410. doi: 10.1038/s41575-019-0134-x - DOI - PubMed
    1. McEnerney L, Duncan K, Bang B-R, Elmasry S, Li M, Miki T, et al. . Dual modulation of human hepatic zonation via canonical and non-canonical wnt pathways. Exp Mol Med (2017) 49:e413. doi: 10.1038/emm.2017.226 - DOI - PMC - PubMed
    1. Cheng ML, Nakib D, Perciani CT, MacParland SA. The immune niche of the liver. Clin Sci (Lond) (2021) 135:2445–66. doi: 10.1042/CS20190654 - DOI - PubMed