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

PLoS One. 2011;6(7):e21949. doi: 10.1371/journal.pone.0021949. Epub 2011 Jul 11.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Interleukin-1beta / pharmacology*
  • Interleukin-2 / metabolism*
  • Interleukin-2 / pharmacology
  • Mice
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism*
  • Thyroglobulin / genetics
  • Thyroglobulin / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Transforming Growth Factor beta1 / pharmacology


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-1beta
  • Interleukin-2
  • Transforming Growth Factor beta1
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Thyroglobulin