NFIL3/E4BP4 is a key transcription factor for CD8α+ dendritic cell development

Masaki Kashiwada, Nhat Long L. Pham, Lecia L. Pewe, John T. Harty, Paul B. Rothman

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Antigen presentation by mature dendritic cells (DCs) is the first step for initiating adaptive immune responses. DCs are composed of heterogeneous functional subsets; however, the molecular mechanisms that regulate differentiation of specific DC subsets are not understood. Here, we report that the basic leucine zipper transcription factor NFIL3/E4BP4 is essential for the development of CD8α+ conventional DCs (cDCs). Nfil3 -/- mice specifically lack CD8α+ cDCs but not CD8α+ cDCs or plasmacytoid DCs in lymphoid tissues. Flt3 ligand-dependent generation of CD8α+ cDCs in lymphoid tissues and CD8α+-equivalent cDCs from Nfil3-/- bone marrow cells was also impaired. NFIL3 regulates CD8α+ cDC development in part through Batf3 expression. Importantly, Nfil3-/- mice exhibited impaired cross-priming of CD8+ T cells against cellassociated antigen, a process normally performed by CD8α+ cDCs, and failed to produce IL-12 after TLR3 stimulation. Thus, NFIL3 plays an essential role in the development of CD8α+ cDCs.

Original languageEnglish (US)
Pages (from-to)6193-6197
Number of pages5
JournalBlood
Volume117
Issue number23
DOIs
StatePublished - Jun 9 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kashiwada, M., Pham, N. L. L., Pewe, L. L., Harty, J. T., & Rothman, P. B. (2011). NFIL3/E4BP4 is a key transcription factor for CD8α+ dendritic cell development. Blood, 117(23), 6193-6197. https://doi.org/10.1182/blood-2010-07-295873