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.

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⁺CD45RB^hi (RB^hi) T cells, with or without CD4⁺CD45RB^lo 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^−/− RB^hi T cells and CD4⁺Foxp3⁺ cells from Foxp3-eGFP mice.

Signaling by type I IFNs was required for maintenance of Foxp3 expression and the suppressive activity of Tregs in mice. Transfer of CD4⁺CD45RB^loCD25⁺ 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.

Type I IFNs regulate intestinal homeostasis by maintaining Foxp3 expression on Tregs in colons of mice under inflammatory conditions.