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

with T and/or B cells. While liver-resident ILCs secrete carbohydrate and dietary fat levels present in the blood that
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IFNγ and tumor necrosis factor (TNF), their cytolytic is supplied to the liver. Within this microenvironment,
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capacity is limited. In comparison to mouse livers, human hepatocytes play a crucial role in metabolic processes. They
livers contain a significantly higher number of NK cells. assimilate carbohydrates and store them as glycogen, while
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The CD49a NK-cell subset is likely the human equivalent dietary fats are transported from the gut as chylomicrons
of mouse liver-resident NK cells, characterized by high and subsequently transformed into various lipoproteins.
levels of CD69 and granzyme B expression, as well as the These lipoproteins, in turn, partake in the distribution of
production of substantial amounts of IFNγ, TNF, and triglycerides and cholesterol throughout the body. Notably,
granulocyte-macrophage colony-stimulating factor. In liver inflammation is closely associated with metabolic
addition, CD56 bright NK cells are particularly abundant dysregulation. 17,18 Metabolites such as succinate, along with
in the liver of humans, constituting over 50% of the total circulating levels of triglycerides and cholesterol, promote
hepatic NK population, compared to only 10 – 15% in TLR signaling and inflammasome activation. Metabolic
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peripheral blood. 12 regulation extends beyond hepatocytes, influencing
macrophages and DCs as well. Upon activation, these
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2.4. T cells and B cells immune cells undergo metabolic reprogramming, shifting
The healthy liver contains lymphocytes of the adaptive from oxidative phosphorylation to aerobic glycolysis, a
immune system, including classic major histocompatibility phenomenon commonly referred to as the Warburg effect.
complex (MHC)-restricted CD4 and CD8 T cells, as well This metabolic switch is essential for the production of pro-
+
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as B cells. CD8 T cells, activated T cells, and memory T inflammatory mediators in macrophages, yet its impact
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cells are particularly abundant in the liver. Interestingly, on KC function in the liver remains an enigma. Under
the liver is known as a site where T cells undergo apoptosis normoxic conditions, the shift to aerobic glycolysis leads
and deletion, earning it the moniker “graveyard” for T cells. to increased levels of succinate, which in turn activates
B cells also comprise a significant portion, up to 8%, of the hypoxia-inducible factor 1 alpha and IL-1β production. 19
total lymphocyte population in the human liver. During The liver’s cellular constituents respond to metabolic
viral infections that specifically target the liver, certain signals that drive inflammation, orchestrating a regulatory
subpopulations of hepatic B cells, such as innate-like CD5 cascade that modulates the activity of liver-immigrating
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B cells, expand further within the liver. immune cell populations. In this dynamic interplay, both
resident immune cells and hepatic cells contribute to the
3. Dynamics of immune responses in generation of inflammation and inflammatory mediators,
the liver microenvironment: Regulation which are vital for upholding local liver function and
between homeostasis and inflammation- overall systemic balance. It becomes evident that liver
associated pathology inflammation is not a static process but a dynamic
network of responses intricately woven to uphold organ
The liver plays a critical role in maintaining overall and systemic equilibrium in healthy individuals. As we
homeostasis, a function largely attributed to its dynamic navigate through the complex web of the liver’s dynamic
environment, which is shaped by a distinctive cytokine and microenvironment, it becomes imperative to comprehend
growth factor milieu. 14-16 The delicate equilibrium between its role in organ homeostasis. This understanding serves
inflammatory response and the maintenance of tolerance in as the key to unraveling the pathological alterations that
a normal liver is intricately regulated by its intricate structure, occur in liver-related disorders, offering insights that can
diverse immune cell composition, and persistent stimulations. pave the way for targeted interventions.
The hepatic blood supply significantly influences the levels of
both pro-inflammatory and anti-inflammatory cytokines. 3.1. Tolerance mechanisms in the liver
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The origins of this cytokine milieu likely stem from the The liver is often considered tolerogenic from an
liver’s typical physiological activities, with this intricate immunological perspective, yet it can generate heightened
balance existing in the absence of pathological infection or immune responses under various circumstances. 20,21
inflammation. Processes such as PRR signaling, induced This concept was first observed in liver transplantation,
by molecules derived from gut contents, also contribute to where recipients typically require lower levels of
maintaining this delicate equilibrium. In addition, activated immunosuppression compared to those receiving other
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hepatic lymphoid immune cell populations play an important organs. In some cases, immunosuppression can be
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role in shaping this milieu. completely discontinued after liver transplantation
Compounding this complexity, the microenvironment without triggering graft rejection. The liver’s remarkable
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in the liver is significantly influenced by the elevated tolerogenic properties are further emphasized by its

Volume 3 Issue 3 (2024) 5 doi: 10.36922/gpd.3186