CD4+ T Cells Play A Role In The Development And Progression Of Liver Disease and Liver Cancer!
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 25, 2024 6 days, 3 hours, 39 minutes ago
Medical News: The Silent Threat: Liver Cancer
Liver cancer is a growing concern worldwide. According to the World Health Organization (WHO), it's the fourth leading cause of cancer-related deaths. Each year, around 906,000 new cases are reported, with approximately 830,000 deaths. Among these, hepatocellular carcinoma (HCC) is the most common type, making up 75% of liver cancer cases. Major causes of HCC include viral infections like hepatitis B and C, alcohol addiction, exposure to dietary toxins, and nonalcoholic fatty liver disease (NAFLD). A more severe form of NAFLD, nonalcoholic steatohepatitis (NASH), is also a significant contributor.
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CD4+ T Cells Play A Role In The Development And Progression Of Liver Disease and Liver Cancer
The role of B cells, DCs, neutrophils, KCs, and CD8+T cells in NASH progression. B-cell-activating factor (BAFF) is involved in B cell activation, and intestinal-derived microbial factors activate B cells in the liver in a manner dependent on myeloid differentiation primary response protein 88 (MyD88). Activated B cells promote NASH progression by regulating CD4+T cell and CD8+T cell activation and the secretion of TNF-α. Both conventional DC1s (cDC1s) and conventional DC2s (cDC2s) are present in the liver and accumulate during NASH progression. cDC1s have been shown to promote liver damage in mice. Neutrophil-derived lipid carrier protein 2 (LCN2) exacerbates steatohepatitis by inducing CXC motif chemokine receptor 2 (CXCR2) expression to promote crosstalk between neutrophils and liver macrophages. Activated Kuffer cells (KCs) promote the recruitment of monocyte-derived macrophages (MoMFs) in a C manner dependent on –C chemokine receptor type 2 (CCR2) by secreting C-C motif ligand 2 (CCL2). MoMFs further amplify the inflammatory response. CD8+T cells, especially CXCR6+ CD8+T cells, directly induce hepatocyte injury and NASH–HCC transition in a perforin-independent and FASL-independent manner. Mice lacking PD-1 showed an increased incidence of liver cancer, which may be due to increased CD8+T cell activation as well as cytokine expression (IFN-γ, TNF-α).
The Role of CD4+ T Cells
CD4+ T cells are a type of immune cell that plays a crucial role in the body's defense mechanisms. They are involved in various immune responses, including those against cancer. A new study covered in this
Medical News report conducted by researchers from Chongqing University-China and Chongqing University Cancer Hospital-China has been focusing on how these CD4+ cells contribute to the development and progression of liver diseases like NASH and HCC.
CD4+ T Cells and NASH
NASH is characterized by the buildup of fat in the liver, leading to inflammation and liver damage. This can progress to liver fibrosis, cirrhosis, and eventually HCC. CD4+ T cells are involved in this process through different subtypes:
-Th1 Cells: These cells produce inflammatory molecules like int
erferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). They are found in higher numbers in the livers of NASH patients, contributing to liver inflammation and tissue damage.
-Th2 Cells: These cells can have both pro-inflammatory and anti-inflammatory effects. They secrete cytokines such as IL-4, IL-5, and IL-13, which can promote tissue repair but also contribute to liver fibrosis.
-Th17 Cells: Known for their role in inflammation, Th17 cells produce IL-17, which has been shown to exacerbate liver damage and fibrosis in NASH.
-Th22 Cells: These cells secrete IL-22, which generally has protective effects against liver damage by promoting tissue repair and reducing inflammation.
-Regulatory T Cells (Tregs): These cells help maintain immune tolerance and prevent excessive inflammation. However, they can also promote liver fibrosis through the secretion of certain factors.
CD4+ T Cells and HCC
As NASH progresses to HCC, the role of CD4+ T cells becomes more complex. They can either promote or inhibit cancer progression:
-Promoting Cancer: In some cases, CD4+ T cells contribute to liver inflammation and damage, creating an environment conducive to cancer development.
-Inhibiting Cancer: On the other hand, CD4+ T cells can also play a role in immune surveillance, helping the body recognize and destroy cancer cells.
Challenges and Therapeutic Potential
Understanding the dual roles of CD4+ T cells in liver disease and cancer is crucial for developing effective therapies. Currently, there are no approved treatments specifically targeting NASH. However, immunotherapy, particularly immune checkpoint inhibitors, shows promise for treating HCC. These therapies aim to enhance the body's immune response against cancer cells.
Conclusion
The increasing prevalence of obesity worldwide has made NASH a leading cause of HCC. CD4+ T cells play significant roles in both diseases, with different subtypes contributing to either disease progression or inhibition. Future research and therapeutic strategies targeting these cells hold potential for better managing and treating NASH and HCC.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/13/6895
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