Type I Interferons Maintain Foxp3 Expression and T-Regulatory Cell Functions Under Inflammatory Conditions in Mice

Background & Aims Foxp3+ T-regulatory cells (Tregs) maintain intestinal homeostasis under conditions of continuous challenge with inflammatory microbes. However, plasticity of the Treg population under certain conditions has been reported; Foxp3+ Tregs can be converted to Foxp3− CD4+ T cells. Methods We used mice with a T cell–induced colitis model to study the regulatory role of type I interferons (IFNs) in adaptive immunity. We transferred CD4+ CD45RBhi (RBhi ) T cells, with or without CD4+ CD45RBlo CD25+ T cells, from wild-type or IFN-αβR −/− mice into Rag1 −/− recipients. We analyzed induction of colitis by flow cytometry, confocal microscopy, and enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction analyses. IFN-αβR −/− Rag −/− mice were given injections of recombinant IFN-α following transfer of IFN-αβR −/− RBhi T cells and CD4+ Foxp3+ cells from Foxp3-eGFP mice. Results Signaling by type I IFNs was required for maintenance of Foxp3 expression and the suppressive activity of Tregs in mice. Transfer of CD4+ CD45RBlo CD25+ Tregs from IFN-αβR −/− mice did not prevent T-cell induction of colitis in mice. Foxp3 expression by Tregs transferred from IFN-αβR −/− mice was significantly lower than that of Tregs from wild-type mice. Administration of recombinant IFN-α reduced T cell–mediated colitis by increasing the number of Foxp3+ Tregs and their suppressive functions. Conclusions Type I IFNs regulate intestinal homeostasis by maintaining Foxp3 expression on Tregs in colons of mice under inflammatory conditions.