Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages

EMBO J. 2011 May 17;30(13):2690-704. doi: 10.1038/emboj.2011.163.

Abstract

Dendritic cells (DCs) have critical roles in the induction of the adaptive immune response. The transcription factors Id2, Batf3 and Irf-8 are required for many aspects of murine DC differentiation including development of CD8α(+) and CD103(+) DCs. How they regulate DC subset specification is not completely understood. Using an Id2-GFP reporter system, we show that Id2 is broadly expressed in all cDC subsets with the highest expression in CD103(+) and CD8α(+) lineages. Notably, CD103(+) DCs were the only DC able to constitutively cross-present cell-associated antigens in vitro. Irf-8 deficiency affected loss of development of virtually all conventional DCs (cDCs) while Batf3 deficiency resulted in the development of Sirp-α(-) DCs that had impaired survival. Exposure to GM-CSF during differentiation induced expression of CD103 in Id2-GFP(+) DCs. It did not restore cross-presenting capacity to Batf3(-/-) or CD103(-)Sirp-α(-)DCs in vitro. Thus, Irf-8 and Batf3 regulate distinct stages in DC differentiation during the development of cDCs. Genetic mapping DC subset differentiation using Id2-GFP may have broad implications in understanding the interplay of DC subsets during protective and pathological immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • CD8 Antigens / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Lineage / genetics*
  • Cells, Cultured
  • Dendritic Cells / metabolism
  • Dendritic Cells / physiology*
  • Gene Expression / physiology
  • Genes, cdc / physiology
  • Inhibitor of Differentiation Protein 2 / genetics*
  • Inhibitor of Differentiation Protein 2 / physiology
  • Integrin alpha Chains / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological

Substances

  • Antigens, CD
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Integrin alpha Chains
  • alpha E integrins