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Gene & Protein in Disease Modulating immune response in liver by curcumin

Thus, the detoxification of blood from the gut by the potency of cytokine production and T cell activation
the liver not only protects the rest of the body from has been attributed to a newly identified sub-population
excessive immune activation but also shapes the unique of human hepatic CD141 DCs. This finding highlights
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immunological environment within the liver. Despite their significant role in immune response modulation.
the recognition of various liver-resident immune cell The infiltration of monocytes and other immune cells
populations, the full range of immune cells residing in the into the liver is extensively influenced by the activities of
liver, especially in humans, remains uncertain. Additional KCs. Once in the liver, these monocytes can differentiate
research is necessary to identify the unique immune into regulatory IL-10 /IL-12 DCs under the influence of
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cell populations within the liver and to characterize hepatocyte growth factor, macrophage colony-stimulating
their distinctive phenotypic features. These resident factor, or low-level LPS stimulation. Plasmacytoid DCs, a
cell populations play crucial roles in maintaining organ specialized population of DCs, are highly abundant in the
homeostasis and regulating inflammation in a healthy liver and play a crucial role in viral defense by producing
adult liver. type I interferons (IFNs). In addition, plasmacytoid DCs
contribute significantly to maintaining liver homeostasis
2.1. Macrophages and KCs through the expression of indoleamine 2,3-dioxygenase,
Macrophages play a crucial role in identifying microbial an enzyme that breaks down l-tryptophan into the
molecules and generating inflammatory mediators immunoregulatory metabolite l-kynurenine. 13
within the body. The liver, in particular, houses
approximately 80% of all macrophages in the body, 2.3. Natural killer (NK) cells and NK T cells
including monocytes. KCs comprise a self-replenishing The adult liver harbors a diverse array of innate lymphocytes
7,8
macrophage population that resides in the liver that possess potent cytokine production capabilities,
independently of the myeloid monocytic compartment. impacting both the innate and adaptive arms of the
These cells originate from resident stem cells derived immune system within the hepatic environment. Among
from the fetal yolk sac. At present, there are no specific these, lymphocyte populations are mucosal-associated
markers available to clearly differentiate human KCs from invariant T cells, NK cells, and NKT cells, including CD1d-
infiltrating monocyte-derived cells. Despite its frequent restricted invariant NKT cell populations. Notably, there
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usage as an indicator for liver-resident macrophages, exists a remarkable disparity in the composition of innate
CD68 alone is insufficient for distinguishing KCs from lymphocytes between the livers of mice and humans. In
monocyte-derived cells. KCs possess an extensive range the human liver, NK cells constitute a significant portion of
of PRRs, complement receptors, and Fc receptors, which the lymphocyte population, accounting for approximately
enable them to exhibit heightened phagocytic activity 30 – 50% of the total. Human NK cells are conventionally
and produce inflammatory cytokines. 9,10 Their roles are divided into two subtypes based on their expression
indispensable in immune regulation, tissue repair, and levels CD56:CD56 low-expressing (CD56dim) NK cells,
liver regeneration. Furthermore, the KC scan responds known for their cytolytic capabilities, and CD56 high-
to signals from cytokines, toll-like receptors (TLRs), expressing (CD56bright) NK cells, which primarily secrete
retinoic acid-inducible gene-I-like receptors, and cytokines that modulate the immune system. 12,13 NK cells
nucleotide oligomerization domain-like receptors. 11,12 are generally considered to have minimal interaction
The constitutive secretion of interleukin (IL)-10 by KCs with the healthy liver; however, they play a crucial role in
in response to lipopolysaccharide (LPS) stimulation, liver inflammation, particularly in antiviral defense. The
coupled with the expression of programmed cell death suppression of NK cell activity in the liver is mediated
1 ligand and the induction of regulatory T (Treg) cells, directly through TLR4 signaling on KCs, which leads to
highlights their role in maintaining homeostasis. In the the secretion of the anti-inflammatory cytokine IL-10, a
liver, human KCs are a significant source of IL-10 during process dependent on myeloid differentiation primary
steady-state conditions, as they actively respond to LPS response 88 signaling. On the other hand, activation of
challenge. 13 TLR2 or TLR3 triggers the production of IL-18 and IL-1β,
thereby activating NK cells. Liver-resident NK cells exhibit
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2.2. Dendritic cells (DCs) distinct characteristics in terms of their source, phenotype,
The liver of healthy individuals contains populations of and role. In mice, hepatic NK cells share similarities with
DCs, specifically myeloid DCs and plasmacytoid DCs. mucosal type 1 innate lymphoid cells (ILCs), as evidenced
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Despite being described as phenotypically immature, by their reliance on T cells and their expression of NK1.1
hepatic DC populations have the ability to mount robust (CD161), NKp46, CD69, and TRAIL. However, hepatic NK
adaptive immune responses. In a recent development, cells do not express DX5 (CD49d) or markers associated
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Volume 3 Issue 3 (2024) 4 doi: 10.36922/gpd.3186