The Role of CD39 in Modulating Effector Immune Responses in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease is associated with excessive inflammation of the bowel and intestinal tissues in genetically susceptible individuals. IBD can manifest in two major forms, ulcerative colitis and Crohn’s disease. T helper type 17 cells (Th17) are effector lymphocytes that have been linked to intestinal inflammation in both mice and humans. Effector Th17 cells and regulatory T cells (Treg) – a subset pivotal to immune-tolerance maintenance – derive from the same CD4 progenitors. Our investigation demonstrates that Th17 cells with suppressor activity (supTh17) can be generated upon induced regulatory T cell (iTreg) exposure to Th17 polarizing conditions. With immune suppressive function that differentiates it from Th17, suppressor Th17 (supTh17) expresses high levels of CD39, a membrane-bound protein that catalyzes conversion of pro-inflammatory extracellular nucleotides into nucleosides, such as adenosine. Interestingly, though supTh17 is detected in the peripheral circulation and lamina propria of healthy subjects, it is diminished in patients with Crohn’s disease. This finding has important clinical implications for the development of innovative therapeutic techniques for targeting inflammation in autoimmune diseases, such as IBD.