Studies by scientists at Main Line Health’s Lankenau Institute for Medical Research (LIMR) identified a key immune regulatory mechanism that may lead to autoimmune diseases, such as rheumatoid arthritis and lupus. The focus of their investigation was on the enzyme IDO2, which recently was found to play a critical role in immunomodulation. But little was known about how exactly it influences autoimmunity.
“Our work demonstrates that IDO2 functions as a modifier in B cells to control pathogenic inflammation and autoimmunity,” wrote the LIMR authors, whose paper was published in the June issue of The Journal of Immunology and listed by the “In This Issue” section, which highlights manuscripts considered to be among the top 10 percent of articles published in the prestigious journal. The researchers found that IDO2’s mechanism of action is to mediate the interaction between T and B cells, and to modulate the potency of T cell help needed to promote autoantibody production in B cells.
“For the first time, we are able to show that IDO2 is acting specifically in B cells, the cell type that produces the autoantibodies required for disease,” stated Lauren Merlo, PhD, research assistant professor and first author of the publication. “This knowledge is critical for developing new strategies that target IDO2 to interfere with the development of autoimmune disorders.”
The need to understand how debilitating autoimmune diseases develop may lead to more effective therapies. Rheumatoid arthritis, for example, is the most common form of autoimmune arthritis, affecting more than 1.3 million Americans. Of those, about 75 percent are women, according to the American College of Rheumatology. And lupus affects approximately 1.5 million Americans, according to the Lupus Foundation of America. People of African, Asian, and Native American descent are more likely to develop lupus than are Caucasians, and 90 percent of those diagnosed with the autoimmune disease are women.
LIMR researchers discovered the IDO2 gene (which expresses the IDO2 enzyme) in 2006. It lies just downstream (on chromosome 8) of a related protein, IDO1, and may be a critical element in immune behavior.
“By demonstrating that IDO2 acts in B cells to induce arthritis, we have uncovered a critical step in the underlying mechanism driving inflammatory autoimmunity, and we identified IDO2 as a potential new therapeutic target to treat rheumatoid arthritis and other antibody-mediated autoimmune diseases,” stated lead author, Laura Mandik-Nayak, PhD, LIMR Associate Professor.
Other LIMR authors of the manuscript include James DuHadaway, Samantha Grabler, George Prendergast, PhD, and Alexander Muller, PhD.