Arc/Arg3.1 defines dendritic cells and Langerhans cells with superior migratory ability independent of phenotype and ontogeny in mice

Eur J Immunol. 2019 May;49(5):724-736. doi: 10.1002/eji.201847797. Epub 2019 Mar 6.


The key function of migratory dendritic cells (migDCs) is to take up antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate immune responses. Recently, we discovered that in the mouse immune system activity-regulated cytoskeleton associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) is exclusively expressed by migDCs and is a central driver of fast inflammatory migration. However, the frequency of Arc/Arg3.1-expressing cells in different migDC subsets and Langerhans cells (LCs), their phylogenetic origin, transcription factor dependency, and functional role remain unclear. Here, we found that Arc/Arg3.1+ migDCs derived from common DC precursors and radio-resistant LCs. We detected Arc/Arg3.1+ migDCs in varying frequencies within each migDC subset and LCs. Consistently, they showed superiority in inflammatory migration. Arc/Arg3.1 expression was independent of the transcription factors Irf4 or Batf3 in vivo. In intradermal Staphylococcus aureus infection that relies on inflammatory antigen transport, Arc/Arg3.1 deletion reduced T-cell responses. By contrast, Arc/Arg3.1 deficiency did not hamper the immune response to systemic Listeria monocytogenes infection, which does not require antigen transport. Thus, Arc/Arg3.1 expression is independent of ontogeny and phenotype and although it is restricted to a small fraction within each migDC subset and LCs, Arc/Arg3.1+ migDCs are important to facilitate infectious migration.

Keywords: Cell trafficking; Dendritic cells; Immune response; Migration; Skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Movement / genetics*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Immunophenotyping
  • Inflammation / etiology
  • Inflammation / metabolism
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism*
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology


  • Biomarkers
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein