Low levels of the enzyme PTPN2 promote the development a group of T-cells with pro-inflammatory properties, contributing to syndromes such as Crohn’s disease, scientists report. Their findings suggest that treatments targeting PTPN2 may help control inflammation in these patients.
The study, “PTPN2 regulates T cell lineage commitment and αβ versus γδ specification,” was published in The Journal of Experimental Medicine.
Variations within the DNA sequence of the tyrosine phosphatase PTPN2 gene were previously linked to a higher risk of developing autoimmune diseases including Crohn’s.
Researchers at Monash University, Australia, reported earlier that the PTPN2 enzyme — a type of protein — plays a key role in the development of T-cells, vital cells of the immune system. The team also discovered that, in low levels, the PTPN2 enzyme led to the development of a particular subset of T-cells that are prone to attacking the body’s own cells and tissues. The mechanism underlying this, however, was not well-understood.
The researchers further explored the role of PTPN2, asking how this enzyme affected the development of two particular subsets of T-cells: the αβ and γδ T-cells. They removed the gene coding for PTPN2 and found that doing so clearly shifted activity toward generating γδ T-cells with pro-inflammatory properties, promoting the development of Crohn’s disease, irritable bowel syndrome (IBS), and rheumatoid arthritis.
“This is an important advance in our understanding of critical checkpoints in T-cell development,” Tony Tiganis, the study’s lead author and a professor at Monash Biomedicine Discovery Institute, said in a press release.
“It helps decide whether the progenitors go on to become T-cells or something else; if they become one type of T-cell or another type,” he added.
These results suggest that drugs regulating PTPN2’s activity may carry positive therapeutic benefits for inflammatory diseases. “There are drugs that target some of these pathways – potentially we might be able to use existing drugs to target these pathways in the context of autoimmune and inflammatory diseases to help a subset of patients with a deficiency in this gene, although that is a long way off,” Tiganis said.
“Understanding the mechanisms that govern early T-cell development and how these are altered in human disease may ultimately afford opportunities for novel treatments. This is very exciting,” the study’s first author, Florian Wiede, said.
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