GM-CSF increases cross-presentation and CD103 expression by mouse CD8⁺ spleen dendritic cells

Eur J Immunol. 2011 Sep;41(9):2585-95. doi: 10.1002/eji.201141540. Epub 2011 Aug 4.

Abstract

Resident CD8(+) DCs perform several functions, including cross-presenting antigen and rapidly engulfing the Gram-positive intracellular pathogen Listeria monocytogenes. Little is known about how these functions of CD8(+) DCs are modulated. Here, we show that granulocyte-macrophage CSF (GM-CSF), a cytokine that exists at low levels at steady state but is elevated during infection and inflammation, enhances cross-presentation and rapid uptake of L. monocytogenes by resident CD8(+) DCs. This previously unrecognized functional enhancement of CD8(+) DCs by GM-CSF was independent of promoting DC survival in vitro. Enhancement of these functions by GM-CSF was also marked by CD103 expression on CD8(+) DCs that was strongly regulated by GM-CSF. Our findings not only identify GM-CSF as a key molecule regulating CD8(+) DC function, but also as a factor responsible for functional heterogeneity of CD8(+) DCs that is at least substantially demarcated by CD103 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • CD8 Antigens / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Cross-Priming / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Gene Expression Regulation / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Immunomodulation
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism*
  • Listeria monocytogenes / immunology*
  • Listeria monocytogenes / pathogenicity
  • Listeriosis / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Spleen / pathology

Substances

  • Antigens, Bacterial
  • Antigens, CD
  • CD8 Antigens
  • Integrin alpha Chains
  • alpha E integrins
  • Granulocyte-Macrophage Colony-Stimulating Factor