IL-1Î² promotes TGF-Î²1 and IL-2 dependent Foxp3 expression in regulatory T cells
Ganesh, Balaji B.
Prabhakar, Bellur S.
PublisherPublic Library of Science
MetadataShow full item record
Earlier, we have shown that GM-CSF-exposed CD8Î±- DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1Î² can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1Î² on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1Î² enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1Î² 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-1Î² 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-1Î² 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-1Î². Further analyses showed that the ability of IL-1Î² to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-Î²1 and IL-2 expression in Foxp3+Tregs and CD25- effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1Î² enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1Î² can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity.