ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.

Dendritic cells (DCs) comprise two major subsets, the interferon (IFN)-producing plasmacytoid DCs (pDCs) and antigen-presenting classical DCs (cDCs). The development of pDCs is promoted by E protein transcription factor E2-2, whereas E protein antagonist Id2 is specifically absent from pDCs. Conversely, Id2 is prominently expressed in cDCs and promotes CD8(+) cDC development. The mechanisms that control the balance between E and Id proteins during DC subset specification remain unknown. We found that the loss of Mtg16, a transcriptional cofactor of the ETO protein family, profoundly impaired pDC development and pDC-dependent IFN response. The residual Mtg16-deficient pDCs showed aberrant phenotype, including the expression of myeloid marker CD11b. Conversely, the development of cDC progenitors (pre-DCs) and of CD8(+) cDCs was enhanced. Genome-wide expression and DNA-binding analysis identified Id2 as a direct target of Mtg16. Mtg16-deficient cDC progenitors and pDCs showed aberrant induction of Id2, and the deletion of Id2 facilitated the impaired development of Mtg16-deficient pDCs. Thus, Mtg16 promotes pDC differentiation and restricts cDC development in part by repressing Id2, revealing a cell-intrinsic mechanism that controls subset balance during DC development. © 2014 Ghosh et al.

Citation

Hiyaa S Ghosh, Michele Ceribelli, Ines Matos, Allan Lazarovici, Harmen J Bussemaker, Anna Lasorella, Scott W Hiebert, Kang Liu, Louis M Staudt, Boris Reizis. ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. The Journal of experimental medicine. 2014 Jul 28;211(8):1623-35

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PMID: 24980046

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