The possible role for FOXP1 protein in the control of autoimmune diseases has been identified

Researchers at the Russian Academy of Sciences' Institute of Bioorganic Chemistry (IBCh RAS) and Memorial Sloan Kettering Cancer Center have created a genetic model to help understand how the body inhibits autoimmune and cancer diseases. The researchers reported their findings in the journal Nature Immunology.

There is an immune system in the human body, which is the most important defense system for the human body to resist pathogens. This system consists of immune organs, immune cells, and immune molecules. The immune system can help humans fight infectious diseases. They can identify pathogens such as viruses, bacteria, fungi, protozoa, and multicellular parasites and kill them.

T lymphocytes, or "helper lymphocytes", are a special type of immune cell. Helper lymphocytes also contain a special lineage called regulatory T cells, or "Tregs," which play an important role in limiting autoimmunity and chronic inflammation. Mutations that interfere with the development and normal functioning of Treg cells can have disastrous consequences for the body. Treg cells have regulatory functions in vitro and in vivo. Lack of or functional inhibition of Treg cells can lead to a variety of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus.

FoxP3, short for Forkhead box P3, as a kind of transcription factors, specific expression in Treg cells; in other words, the production of Treg cells are regulated by the transcription factor FoxP3. The scientists studied the FoxP3 protein, which is critical to the development and inhibitory function of Treg cells. They found that removing the FoxP3 gene from genomic DNA through genetic engineering prevented Treg cells from developing, leading to the death of the organisms.

In fact, if FoxP3 stops working, the body can not generate Treg cells. In this case, ordinary T cells will destroy human organs, causing a variety of autoimmune diseases. Moreover, it has been reported that the function of Treg is also affected in the occurrence of enteritis, rheumatoid arthritis, multiple sclerosis, lupus, and other diseases. FoxP3 is part of a protein complex that helps regulate the function of genes necessary for Treg cells to function properly, rather than acting alone. This group of proteins includes FoxP1, which has been the subject of less research.

The researchers designed a genetic model that allows them to explain exactly how FoxP1 affects FoxP3. They first removed the FoxP1 gene from the Treg in laboratory mice and compared it with "normal" cells. They found that FoxP3 binds to DNA worse in the absence of FoxP1. In other words, without FoxP1, the protein genes that are essential for the proper functioning of Treg cells do not work properly. Therefore, if FoxP3 is important for Treg, then FoxP1 is also crucial because its removal negatively affects FoxP3. So the key to making drugs that selectively affect Treg cells is to understand the structure of the protein complex that contains FoxP3 and FoxP1.

It has been reported that the presence or absence of FoxP3 and Treg cells is directly related to the prognosis of ovarian cancer. It has been found that FoxP3 and Treg at the tumor site can inhibit the body's anti-tumor immune response and thus reduce the survival rate of patients. In addition, the number of FoxP3 and Treg in both peripheral blood and tumor infiltration site was highly correlated with the prognosis of breast cancer patients. From the central role of FoxP3 in Treg inhibition, the expression of FoxP3 by some tumor cells seems to suppress the immune response to tumor cells, causing the immune escape of tumor cells.

The findings significantly expand our understanding of the molecular mechanisms of immune tolerance that can be used to treat cancer and autoimmune diseases. Cancerous tumors attract Treg cells to fight off the body's immune system. The more Treg cells present in the tumor, the worse the prognosis. Therefore, if a drug can be designed to reduce the number and activity of Treg cells in the case of tumors, and conversely, to increase their number and activity in the case of autoimmune diseases, it will be beneficial for many of the hitherto incurable diseases are welcome news.