Regulatory T cells maintain a balanced immune response, preventing autoimmunity, asthma, and allergic reactions. A paper posted yesterday in Nature suggests these T cells are vulnerable to exhaustion that disrupts their normal functioning and may contribute to allergic reaction.
Researchers at St. Jude Children's Research Hospital looked at liver kinase B1 (LKB1), a protein that controls cell growth and metabolism. In a mouse model, researchers were able to show that loss of LKB1 in regulatory T cells disrupted cell metabolism and function. The mice developed fatal inflammatory disease and their regulatory T cells showed changes characteristic of functional exhaustion at the molecular level. This points to T cell exhaustion as a possible cause of allergic reaction, known as the Th2 response.
"The research suggests a possible new therapeutic approach to autoimmune disorders that would be designed to boost the function of regulatory T cells by modulating cell metabolism," said corresponding author Hongbo Chi, Ph.D., a member of St. Jude department of immunology.
The researchers explained that healthy regulatory T cells are able to dampen Th2 response in part through LKB1's ability to restrain expression of the cell surface receptor PD-1 and possibly other receptors. When active, PD-1 inhibits the activity of T cells and the immune response in order to prevent autoimmune disorders.
Loss of LKB1 can lead to overproduction of PD-1, limiting the ability of regulatory T cells to block Th2 response. Blocking PD-1 in LKB1 deficient mice largely restored the ability to prevent Th2 allergic reaction. Loss of LKB1 was also found to affect Th2 response by repressing cell surface molecules on dendritic cells, thus fueling an allergic reaction.