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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): cytokines T cells
Abstract: Earlier, we have shown that GM-CSF-exposed CD8a2 DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1b can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1b on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1b enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1b and IL-12 had only a modest effect on Foxp32 expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1b 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-1b 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-1b. Further analyses showed that the ability of IL-1b to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-b1 and IL-2 expression in Foxp3+Tregs and CD252 effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1b enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1b 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), e21949. 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. DOI: 10.1371/journal.pone.0021949
URI: http://hdl.handle.net/10027/8510
ISSN: 1932-6203
Date Available in INDIGO: 2012-08-16
 

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