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

ability to induce systemic tolerance in co-transplanted By preferentially suppressing this immune response,
organs. Resident myeloid cells play a crucial role in curcumin helps to eliminate or suppress effector CD4
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maintaining hepatic tolerance. KCs produce anti- and CD8 T cells and promotes the differentiation of naïve
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inflammatory cytokines such as IL-10 and prostaglandins, T cells into Treg cells. The activation of CD4 T cells by
which downregulate the expression of co-stimulatory LSECs might be influenced by IL-10 secretion and the
molecules on antigen-presenting cells (APCs). This decreased expression of MHC class II, CD80, and CD86
process curbs CD4 T cell activation, thereby limiting on LSECs. Furthermore, the liver could induce peripheral
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the adaptive immune response. 23-27 Hepatic myeloid DCs immune tolerance through clonal deletion or apoptosis of
and plasmacytoid cells exhibit reduced potency in T cell antigen-specific T cells.
activation and produce significantly more IL-10 compared
to their splenic counterparts. 28-31 Both hepatocytes and 3.2. Acute phase response (APR) and maintenance of
LSECs are capable of directly presenting antigens to T systemic homeostasis
cells, and hepatic stellate cells (HSCs) may also participate The liver synthesizes various proteins, including
in direct antigen presentation to T cells, influencing the complement proteins and albumin, to maintain systemic
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outcome of immune-regulatory responses. The absence homeostasis. Hepatocytes in the liver are activated when
of co-stimulatory molecules and the limited involvement cytokines from immune cells infiltrate the bloodstream,
of CD4 T cell assistance during antigen presentation triggering a cascade of responses. The APR is a multifaceted
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impede efficient T-cell differentiation in the liver, resulting and rapid reaction aimed at addressing inflammatory
in a bias toward T cell tolerance. 33-35 Regulatory myeloid challenges. During the APR, hepatocytes significantly
populations, notably myeloid-derived suppressor cells increase the production of acute-phase proteins and
(MDSCs), further facilitate the maintenance of the synthesize IL-6, a pivotal cytokine that amplifies the APR.
liver’s tolerogenic environment. MDSCs produce In addition, the APR incorporates mechanisms to restrain
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immunosuppressive cytokines, arginase, and indoleamine excessive inflammation and minimize collateral damage.
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2,3-dioxygenase, which limit immune cell activation and For instance, protease inhibitors, such as α2-macroglobulin
proliferation, enhancing the liver’s immunoregulatory inhibit neutrophil function, while C-reactive protein
potential. In essence, the liver’s status as an immunologically inhibits TNF production from KCs. The APR involves
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tolerant organ is maintained through a complex interplay of sophisticated processes aimed at orchestrating a balanced
resident myeloid cells, hepatocytes, and non-professional immune response, such as the recruitment of suppressive
APCs, creating a finely tuned microenvironment that MDSC populations, through the synthesis of serum proteins
fosters immune tolerance while permitting rapid and and responsiveness to inflammatory signals. Nitric oxide
robust immune responses when necessary. In the (NO) plays a crucial role as a regulatory agent throughout
physiological state of the liver, DCs remain in an immature various stages of inflammation development. It controls
developmental stage, and reticuloendothelial cells produce the pro-inflammatory characteristics of the endothelium
high levels of anti-inflammatory cytokines. As a result, the and regulates the initial phases of inflammatory cell
ability of APCs to activate effector T cells is reduced, leading migration toward the inflamed site. Furthermore, NO
to the generation of anergic T cells and Treg cells. Recent serves as a potent immunoregulatory agent, demonstrating
research has shown that the extract of the turmeric rhizome anti-apoptotic effects by inhibiting the expression of
can boost the levels of both Th1 (IL-2 and IFN-γ) and Th2 developmental genes and cellular proliferation. Its
(IL-10) cytokines, suggesting its dual role in immune anti-inflammatory properties are also attributed to its
regulation. In addition, the polysaccharide fraction of this antioxidant properties. NO exerts modulatory effects on
rhizome has exhibited potent immunostimulatory activity inflammation and immunoregulation by interacting with
by increasing the proliferation of splenocytes and the various transcription factors and signal transduction
secretion of IL-10. The polysaccharides in turmeric extract pathways. Similarly, serum amyloid A modulates
could potentially trigger the proliferation and release of lipoprotein transport and metabolism during the APR,
cytokines in murine splenocytes. Various studies have facilitating the localization of immune cells to inflammation
demonstrated that polysaccharide-enriched fractions can sites and demonstrating a protective effect against tissue
influence the production of cytokines such as transforming damage resulting from oxidation. Haptoglobin, another
growth factor beta (TGF-β), TNF-α, granulocyte- positive acute-phase protein, functions as a scavenger of
macrophage colony-stimulating factor, IL-1α, IL-5, IL-6, hemoglobin. When haptoglobin binds to free hemoglobin,
IL-8, IL-10, IL-13, and others. Curcumin, a component of it promotes phagocytosis by macrophages, blocks the
turmeric, plays a role in preserving the liver’s tolerogenic oxidative properties of hemoglobin, and facilitates the
nature by targeting adaptive immunity mediated by APCs. recycling of iron within the heme. Ceruloplasmin serves

Volume 3 Issue 3 (2024) 6 doi: 10.36922/gpd.3186