Liver: An organ with predominant innate immunity : Hepatology (original) (raw)

Review

1 Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD

2 Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China

*Address reprint requests to: Section on Liver Biology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2S-33, Bethesda, MD 20892

Email:[email protected]

Received 20 June 2007; Accepted 5 September 2007

Published online in Wiley InterScience (www.interscience.wiley.com).

Potential conflict of interest: Nothing to report.

fax: 301-480-0257

Abstract

Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and γδ T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components. Conclusion: The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder. (Hepatology 2007.)

Abbreviations: α1-CPI, α1-cysteine proteinase inhibitor; α2M, α2-macroglobulin; AAP, acute phase protein; AAT, antitrypsin; ACT, antichymotrypsin; C1-INH, C1 inhibitor; CRP, C-reactive protein; CTC, connective tissue component; HBV, hepatitis B virus; HCV, hepatitis C virus; HSC, hepatic stellate cell; IFN, interferon; Ig, immunoglobulin; IL, interleukin; LBP, lipopolysaccharide-binding protein; LEAP, liver-expressed antimicrobial peptide; LPS, lipopolysaccharide; MAp19, mannan-binding lectin-associated protein 19; MASP, mannan-binding lectin-associated serine protease; MBL, mannan-binding lectin; MHC, major histocompatibility complex; NK, natural killer; NKT, natural killer T; NOD, nucleotide-binding oligomerization domain; NS, nonstructural protein; PAMP, pathogen-associated molecular pattern; PGLYP2, peptidoglycan-recognition protein-2; PGRP, peptidoglycan-recognition protein; PRR, pattern-recognition receptor; RAE-1, retinoic acid early inducible gene 1; SAP, serum amyloid P; SPRR, secreted pattern-recognition molecule; TCR, T cell receptor; TGF-β, transforming growth factor β; TLR, toll-like receptor; TNF-α, tumor necrosis factor α; TRAIL, tumor necrosis factor–related apoptosis-inducing ligand.