Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization

PLoS One. 2011;6(10):e25660. doi: 10.1371/journal.pone.0025660. Epub 2011 Oct 17.

Abstract

Dendritic cells (DCs) subsets differ in precursor cell of origin, functional properties, requirements for growth factors, and dependence on transcription factors. Lymphoid-tissue resident CD8α(+) conventional DCs (cDCs) and CD11b(low/-)CD103(+) non-lymphoid DCs are developmentally related, each being dependent on FMS-like tyrosine kinase 3 ligand (Flt3L), and requiring the transcription factors Batf3, Irf8, and Id2 for development. It was recently suggested that granulocyte/macrophage colony stimulating factor (GM-CSF) was required for the development of dermal CD11b(low/-)Langerin(+)CD103(+) DCs, and that this dermal DC subset was required for priming autoreactive T cells in experimental autoimmune encephalitis (EAE). Here, we compared development of peripheral tissue DCs and susceptibility to EAE in GM-CSF receptor deficient (Csf2rb(-/-)) and Batf3(-/-) mice. We find that Batf3-dependent dermal CD11b(low/-)Langerin(+) DCs do develop in Csf2rb(-/-) mice, but that they express reduced, but not absent, levels of CD103. Further, Batf3(-/-) mice lacking all peripheral CD11b(low/-) DCs show robust Th cell priming after subcutaneous immunization and are susceptible to EAE. Our results suggest that defective T effector priming and resistance to EAE exhibited by Csf2rb(-/-) mice does not result from the absence of dermal CD11b(low/-)Langerin(+)CD103(+) DCs.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Surface / metabolism
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD11b Antigen / metabolism*
  • CD8 Antigens / metabolism
  • Cross-Priming / drug effects*
  • Cytokine Receptor Common beta Subunit / deficiency
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dermis / immunology
  • Dermis / pathology
  • Disease Susceptibility
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Immunization*
  • Integrin alpha Chains / metabolism
  • Lectins, C-Type / metabolism
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mannose-Binding Lectins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myelin Proteins / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Repressor Proteins / metabolism*
  • Signal Transduction / drug effects
  • Spleen / drug effects
  • Spleen / immunology
  • Subcutaneous Tissue / drug effects
  • Subcutaneous Tissue / immunology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Antigens, CD
  • Antigens, Surface
  • Basic-Leucine Zipper Transcription Factors
  • CD11b Antigen
  • CD8 Antigens
  • CD8alpha antigen
  • Cd207 protein, mouse
  • Cytokine Receptor Common beta Subunit
  • Integrin alpha Chains
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Repressor Proteins
  • SNFT protein, mouse
  • alpha E integrins
  • Granulocyte-Macrophage Colony-Stimulating Factor