Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease

Regulatory T (T-reg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in T-reg cells was required to suppress development of fatal inflammatory disease. We found that T cell antigen receptor (TCR)-driven signaling initially decreased the abundance of Id3, which led to the activation of a follicular regulatory T (T-FR) cell-specific transcription signature. However, sustained lower abundance of Id2 and Id3 interfered with proper development of T-FR cells. Depletion of Id2 and Id3 expression in T-reg cells resulted in compromised maintenance and localization of the T-reg cell population. Thus, Id2 and Id3 enforce T-FR cell checkpoints and control the maintenance and homing of T-reg cells.