Fibrinogen-like protein 1, known as FGL1, is a protein with emerging importance in scientific research. It plays a significant role in immune function and various diseases. Understanding FGL1 offers insights into how our immune system is regulated and how disruptions in this regulation can contribute to health challenges. Researchers are exploring FGL1’s potential for new medical approaches.
Understanding FGL1
FGL1, or Fibrinogen-like protein 1, is a protein structurally similar to fibrinogen, a well-known protein involved in blood clotting. It is classified as a hepatokine, indicating that it is primarily produced and secreted by the liver.
FGL1 exists in various forms, known as splice variants, which are slightly different versions of the protein. While its primary expression is in the liver, low levels of FGL1 have also been observed in other tissues, such as brown and white adipose tissue, and in the pancreas.
FGL1’s Role in Immune Control
FGL1 suppresses immune responses. Its main mechanism involves binding to and activating Lymphocyte-activation gene 3 (LAG-3), a regulatory protein found on the surface of T cells. This interaction is a type of “immune checkpoint,” a natural brake on the immune system that prevents overactivity and damage to healthy tissues.
When FGL1 binds to LAG-3, it sends inhibitory signals to T cells, white blood cells that identify and eliminate threats. This binding leads to the suppression of T cell activity and proliferation. The FGL1-LAG-3 interaction also affects Natural Killer (NK) cells, another immune cell type involved in early defense against infections and tumors.
FGL1 and Cancer Progression
FGL1 contributes to the development and progression of certain cancers, especially hepatocellular carcinomas. Hepatocyte-derived FGL1 promotes liver metastasis and tumor growth. It achieves this by inhibiting the functions of specific anti-tumor immune cells.
FGL1 suppresses the activity of CD8+ T cells and NK cells, both of which are crucial for detecting and destroying cancer cells. By putting a “brake” on these immune cells, FGL1 allows cancer cells to evade the body’s immune surveillance. This creates an environment where the tumor can thrive and spread within the liver.
Targeting FGL1 for Treatment
Given its role in immune suppression, targeting FGL1 has shown promise as a potential treatment strategy. Blocking the interaction between FGL1 and LAG-3 has demonstrated therapeutic effects in mouse models. This blockade has been shown to restrain liver metastasis and slow tumor growth, leading to prolonged survival in tumor-bearing mice.
The anti-tumor effects observed when FGL1 is blocked are dependent on the presence and activity of both CD8+ T cells and NK cells. This indicates FGL1’s impact on cancer progression is directly linked to its ability to suppress these immune cells. Research into targeting FGL1 is currently exploring its potential in cancer immunotherapy and for treatments aimed at reducing inflammation.