Transcription factor Etv6 regulates functional differentiation of cross-presenting classical dendritic cells

J Exp Med. 2018 Sep 3;215(9):2265-2278. doi: 10.1084/jem.20172323. Epub 2018 Aug 7.


An IRF8-dependent subset of conventional dendritic cells (cDCs), termed cDC1, effectively cross-primes CD8+ T cells and facilitates tumor-specific T cell responses. Etv6 is an ETS family transcription factor that controls hematopoietic stem and progenitor cell (HSPC) function and thrombopoiesis. We report that like HSPCs, cDCs express Etv6, but not its antagonist, ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors. Deletion of Etv6 in the bone marrow impaired the generation of cDC1-like cells in vitro and abolished the expression of signature marker CD8α on cDC1 in vivo. Moreover, Etv6-deficient primary cDC1 showed a partial reduction of cDC-specific and cDC1-specific gene expression and chromatin signatures and an aberrant up-regulation of pDC-specific signatures. Accordingly, DC-specific Etv6 deletion impaired CD8+ T cell cross-priming and the generation of tumor antigen-specific CD8+ T cells. Thus, Etv6 optimizes the resolution of cDC1 and pDC expression programs and the functional fitness of cDC1, thereby facilitating T cell cross-priming and tumor-specific responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • CD8 Antigens / genetics
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • ETS Translocation Variant 6 Protein
  • Gene Deletion
  • Gene Expression Regulation / immunology*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / pathology
  • Immunity, Cellular*
  • Mice
  • Mice, Knockout
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / immunology
  • Proto-Oncogene Proteins c-ets / genetics
  • Proto-Oncogene Proteins c-ets / immunology*
  • Repressor Proteins / genetics
  • Repressor Proteins / immunology*
  • Thrombopoiesis / genetics
  • Thrombopoiesis / immunology


  • Antigens, Neoplasm
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Ets1 protein, mouse
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins