Batf3 selectively determines acquisition of CD8+ dendritic cell phenotype and function

Immunol Cell Biol. 2017 Feb;95(2):215-223. doi: 10.1038/icb.2016.83. Epub 2016 Nov 29.

Abstract

Batf3 is a transcription factor that impacts the development of CD103+ tissue-resident dendritic cells (DCs). However, whether Batf3 is absolutely required for the development of CD8+ DCs remains controversial. Id2 is required for CD8+ DC development. Here we show that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. In contrast, Batf3-/- mice remained competent for skin graft rejection and delayed hypersensitivity, and retained a CD8+ DC population with markers characteristic of the CD11b+ DC lineage, including CD11b, CD4 and CD172α, as well as the key regulator transcription factor IRF4, but lacked IRF8 expression. CD8+ DCs in Batf3-/- mice took up and cleaved protein antigen and larger particles but were unable to phagocytose dying cells, a characteristic feature to the CD8+ DC lineage. These data clarify a requirement for CD8+ lineage DCs to induce effectors of neo-antigen-driven skin graft rejection, and improve our understanding of DC subtype commitment by demonstrating that in the absence of Batf3 CD8+ DCs can change their fate and become CD11b+ DCs.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens / metabolism
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD8 Antigens / metabolism*
  • Cell Lineage
  • Dendritic Cells / immunology*
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / pathology
  • Interferon Regulatory Factors / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis
  • Phenotype
  • Repressor Proteins / metabolism*
  • Skin Transplantation

Substances

  • Antigens
  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • Interferon Regulatory Factors
  • Repressor Proteins
  • SNFT protein, mouse
  • interferon regulatory factor-4
  • interferon regulatory factor-8