Abstract
Abstract T regulatory cells (Treg) play a critical role in maintaining immune homeostasis and tolerance to self-antigen. A subset of Treg induced by activation in the presence of TGF-β (induced or iTreg) has been shown to play a role in regulating immune responses and preventing autoimmune disease (AID). IL-21 is a pleiotropic cytokine involved in both innate and adaptive immune responses. Recent data in mouse models has shown that modulation of IL-21 function can influence Treg development and function, but the effect of IL-21 on human Treg is unknown. Therefore, we investigated the role of IL-21 in development of iTreg from T cells from healthy control (HC) and Crohn’s disease (CD) patients. Induced Treg were generated from CD4+CD25- T cells by activation in the presence of IL-2 and TGFβ. Exogenous IL-21 or blocking anti-IL-21 monoclonal antibody was also included on day 0 and cells were stained for intracellular IL-21 and FoxP3 expression on day 7. There was a significant reduction in the number of Foxp3+ T cells (p<0.03) in the presence of exogenous IL-21 and a significant increase when anti-IL-21 antibody was included (p<0.02). These effects on iTreg development were seen in both HC and CD patients. These data suggest targeting IL-21 with neutralizing antibodies can increase iTreg development and hence has promising potential as a novel therapeutic approach for the treatment of AID such as CD.
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