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J Exp Med. 2014 Jul 28;211(8):1623-35. doi: 10.1084/jem.20132121. Epub 2014 Jun 30.

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

Author information

1
Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
2
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
3
Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
4
Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032.
5
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
6
Department of Microbiology and Immunology, Center for Computational Biology and Bioinformatics, Institute for Cancer Genetics, Department of Pathology, and Department of Pediatrics, Columbia University Medical Center and Department of Biological Sciences and Department of Electrical Engineering, Columbia University, New York, NY 10032 bvr2101@columbia.edu.

Abstract

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.

PMID:
24980046
PMCID:
PMC4113936
DOI:
10.1084/jem.20132121
[Indexed for MEDLINE]
Free PMC Article

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