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

Background & AimsFoxp3+ 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.MethodsWe 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.ResultsSignaling by type I IFNs was required for maintenance of Foxp3 expression and the suppressive activity of Tregs in mice. Transfer of CD4+CD45RBloCD25+ 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.ConclusionsType I IFNs regulate intestinal homeostasis by maintaining Foxp3 expression on Tregs in colons of mice under inflammatory conditions.