Abstract
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses. How the various antigen-presenting cell (APC) populations contribute to this process and how they handle danger signals determine the outcome of the generated immune responses. Importantly, liver mounted responses convey consequences not only for the local but also to systemic immunity. Here, we discuss various aspects of antigen presentation and its consequences by the non-professional APCs in the liver microenvironment.
Highlights
The liver is the metabolic center of the body that is critical for maintaining homeostasis
In the liver microenvironment a complex network of various cell populations ensures the control of T-cell responses
An extensive regulatory apparatus in a bystander manner ensures the maintenance of the tolerogenic milieu in the liver (Figure 1)
Summary
The liver is the metabolic center of the body that is critical for maintaining homeostasis. It perpetuates a tolerogenic environment, is involved in peripheral tolerance, e.g., against food-derived antigens, and carries various immunological functions affecting the local and the systemic immunity (1–3) To fulfill such diverse roles, the liver is provided with blood by the hepatic artery as well as by the portal vein (4). The portal vein carries nutrient rich blood from the gut but it contains molecules/antigens derived from the digested food and the gut microbiome (5) In such exposed microenvironment, it is critical how the liver handles antigens and danger signals and how it allows the maintenance of the tolerogenic milieu while staying alert and ensuring the generation of liver-protecting T-cell responses. Presentation and its consequences by non-professional APCs in the liver
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