IL-1[beta] Promotes TGF-[beta]1 and IL-2 Dependent Foxp3 Expression in Regulatory T Cells

Earlier, we have shown that GM-CSF-exposed CD8[alpha]- DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1[beta] can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1[beta] on Foxp3 expression in T cells when...

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Bibliographic Details
Published in:PloS one 2011-07, Vol.6 (7), p.e21949
Main Authors: Ganesh, Balaji B, Bhattacharya, Palash, Gopisetty, Anupama, Sheng, Jianrong, Vasu, Chenthamarakshan, Prabhakar, Bellur S
Format: Article
Language:English
Subjects:
Analysis
Autoimmunity
Bone morphogenetic proteins
Cytokines
T cells
Transforming growth factors
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Summary:Earlier, we have shown that GM-CSF-exposed CD8[alpha]- DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1[beta] can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1[beta] on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1[beta] enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1[beta] 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-1[beta] 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-1[beta] 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-1[beta]. Further analyses showed that the ability of IL-1[beta] to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-[beta]1 and IL-2 expression in Foxp3+Tregs and CD25- effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1[beta] enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1[beta] can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0021949