The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.
Induced regulatory T cells (iT(reg) 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 iT(reg) cells remain unknown. We report a critical role for the transcription cofactor homeodomain-only protein (Hop; also known as Hopx) in iT(reg) cells to mediate T cell unresponsiveness in vivo. Hopx-sufficient iT(reg) cells downregulated expression of the transcription factor AP-1 complex and suppressed other T cells. In the absence of Hopx, iT(reg) 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 T(reg) cells induced by DCs and the promotion of DC-mediated T cell unresponsiveness in vivo.
Hawiger
Daniel
D
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Wan
Yisong Y
YY
Eynon
Elizabeth E
EE
Flavell
Richard A
RA
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018398:Homeodomain Proteins; C466740:Hop protein, mouse; D018808:Transcription Factor AP-1
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