Immune Functioning in Non lymphoid Organs: The Liver

Abstract

The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are important in the nonspecific cell killing that is important in resistance to tumor cell invasion. The liver has a major role in deletion of activated T cells and induction of tolerance to ingested and self-antigens. Disposal of waste molecules generated through inflammatory, immunologic, or general homeostatic processes is accomplished via the action of specific endocytic receptors on sinusoidal endothelial cells of the liver. Age-related changes in sinusoids (pseudocapillarization), autophagy, and functions of various hepatic cell populations result in substantial alterations in many of these immunologically important functions.

Differential Regulation of Hepatic Organic Cation Transporter 1, Organic Anion-Transporting Polypeptide 1a4, Bile-Salt Export Pump, and Multidrug Resistance-Associated Protein 2 Transporter Expression in Lymphocyte-Deficient Mice Associates with Interleukin-6 Production

“…Since altered Mrp3 and Bsep mRNA expression in response to lymphocyte deficiency was evident only during inflammation, we speculate that lymphocytes likely gain access, via direct contact or through the secretion of soluble mediators, to hepatocytes at times when the vasculature in the liver is inflamed, as the sinusoidal endothelium is highly fenestrated and lacks a basement membrane. In agreement, the sinusoidal membrane has previously been identified as a unique means by which the liver is able to differentially regulate immune-mediated responses (Crispe, 2012;Parker and Picut, 2012). This line of reasoning is also consistent with our observation that lymphocytes retain the capacity to modulate efflux transporters that are located on the apical membrane, i.e., Mrp3, in the absence of LPS-induced inflammation.…”

“…NKT cells represent a population of unconventional T lymphocytes that can mediate both innate and adaptive immune responses and are abundant in the liver (Eberl et al, 1999;Duwaerts and Gregory, 2011;Parker and Picut, 2012). In mice, NKT cells represent approximately 0.5% of the total T cell population in the blood, peripheral lymph nodes, and spleens.…”

Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance

“…Furthermore, immunofluorescence tests showed that the isolated cells were strongly positive for ED-1 and ED-2, which are markers of rat macrophages [22]. Phagocytic activity, a functional characteristic of KCs, was analyzed based on the uptake of Dil-LDL and latex beads.…”

Liver-inherent immune system: its role in blood-stage malaria

“…Less known is the fact that the liver also plays a key immunoregulatory role (Selmi et al, 2007; Crispe, 2009; Nemeth et al, 2009; Parker and Picut, 2012). Indeed, the fetal liver is the primary hematopoietic organ of mammals, and, postnatally, the liver has retained the capability to exert important functions of both innate and adaptive immunity (Parker and Picut, 2012). …”