AsianScientist (Nov. 30, 2018) – A research team at the Academy of Immunology and Microbiology of the Institute for Basic Science (IBS), South Korea, has discovered a key regulator of the immune system which could be a useful therapeutic target. Their findings are reported in Nature Communications.
The immune system can protect the body from invading pathogens, but it can also over-react and cause allergies and autoimmunity. In this respect, regulatory T (Treg) cells are an important built-in ‘self-checking’ mechanism of the immune system—they prevent excessive immune reactions from happening. Conversely, in cancer therapy, Treg cells would need to be restrained to enhance the anti-tumor immune response.
There are two broad categories of Treg cells in mammals: thymic Treg cells (tTreg) and induced Treg cells (iTreg). tTreg cells are generated at a neonatal stage in the thymus and protect the fetus from autoimmune reactions. On the other hand, iTreg cells are formed later in life and accumulate predominantly at mucosal barriers, such as in the intestine and lungs.
In the present study, researchers led by Dr. Dipayan Rudra of IBS have identified a protein called Foxp1 that regulates the formation of iTreg cells. They demonstrated that Foxp1 modifies the expression of the Foxp3 gene that gives Treg cells their identity. iTreg cells lacking Foxp1 gradually lose Foxp3 and become unable to perform their inhibitory functions against overt immune reactions.
In mice, the lack of Foxp1 in iTreg cells led to intestinal inflammation and increased susceptibility to colitis. Moreover, the researchers showed that Foxp1 is essential for sustaining optimal expression of Foxp3 specifically in iTreg cells, not in tTreg cells.
“The results suggest that this protein [Foxp1] could be used to engineer more stable iTreg cells, while keeping their thymic counterparts untouched,” said Rudra.
With this knowledge, scientists could search for drugs that target Foxp1, increasing or decreasing its expression and activity. Such drugs would be useful for the treatment of autoimmune disorders, in addition to being relevant to tumor immunology.
The article can be found at: Ghosh et al. (2018) The Transcription Factor Foxp1 Preserves Integrity of an Active Foxp3 Locus in Extrathymic Treg Cells.
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Source: Institute for Basic Science; Photo: Shutterstock.
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