The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell–mediated peripheral T cell unresponsiveness

Abstract

Induced regulatory T cells help maintain peripheral tolerance. Flavell and colleagues show that the transcription cofactor Hopx is essential in maintaining the anergy and function of these cells. Induced regulatory T cells (iTreg cells) can be generated by peripheral dendritic cells (DCs) that mediate T cell unresponsiveness to rechallenge with antigen. The molecular factors required for the function of such iTreg cells remain unknown. We report a critical role for the transcription cofactor homeodomain-only protein (Hop; also known as Hopx) in iTreg cells to mediate T cell unresponsiveness in vivo. Hopx-sufficient iTreg cells downregulated expression of the transcription factor AP-1 complex and suppressed other T cells. In the absence of Hopx, iTreg cells had high expression of the AP-1 complex, proliferated and failed to mediate T cell unresponsiveness to rechallenge with antigen. Thus, Hopx is required for the function of Treg cells induced by DCs and the promotion of DC-mediated T cell unresponsiveness in vivo.