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IL-1β promotes TGF-β1 and IL-2 dependent Foxp3 expression in regulatory T cells

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Title: IL-1β promotes TGF-β1 and IL-2 dependent Foxp3 expression in regulatory T cells
Author(s): Ganesh, Balaji B.; Bhattacharya, Palash; Gopisetty, Anupama; Sheng, Jianrong; Vasu, Chenthamarakshan; Prabhakar, Bellur S.
Subject(s): T cells immunity
Abstract: Earlier, we have shown that GM-CSF-exposed CD8α- DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1β can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1β on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1β enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1β and IL-12 had only a modest effect on Foxp3- expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1β or IL-12 showed highly significant increase and decrease in Foxp3+ T cell frequencies respectively suggesting direct effects of these cytokines on T cells and a role for IL-1β in promoting Foxp3 expression. Importantly, purified CD4+CD25+ cells showed a significantly higher ability to maintain Foxp3 expression when activated in the presence of IL-1β. Further analyses showed that the ability of IL-1β to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-β1 and IL-2 expression in Foxp3+Tregs and CD25- effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1β enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1β can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity.
Issue Date: 2011-07-11
Publisher: Public Library of Science
Citation Info: Ganesh, B. B., Bhattacharya, P., Gopisetty, A., Sheng, J., Vasu, C., & Prabhakar, B. S. 2011. IL-1β promotes TGF-β1 and IL-2 dependent Foxp3 expression in regulatory T cells. PLoS One, 6(7). DOI: 10.1371/journal.pone.0021949.
Type: Article
Description: © 2011 Ganesh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The original version is available through Public Library of Science at DOI: 10.1371/journal.pone.0021949.
ISSN: 1932-6203
Sponsor: This work was supported by The National Institutes of Health grant RO1 AI058190 to BSP and NIH R01AI073858 to CV and by the University of Illinois at Chicago (UIC) Center for Clinical and Translational Science (CCTS), Award Number UL1RR029879 from the National Center For Research Resources.
Date Available in INDIGO: 2012-08-15

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