| First Author | Ghosh HS | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 8 | Pages | 1623-35 |
| PubMed ID | 24980046 | Mgi Jnum | J:214727 |
| Mgi Id | MGI:5603940 | Doi | 10.1084/jem.20132121 |
| Citation | Ghosh HS, et al. (2014) ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. J Exp Med 211(8):1623-35 |
| abstractText | 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. |
