GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells

Immunity. 2012 Jun 29;36(6):1031-46. doi: 10.1016/j.immuni.2012.03.027.

Abstract

GM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103(+) DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103(+) and CD11b(+) DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8(+) T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8(+) T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Lineage
  • Cytokine Receptor Common beta Subunit / antagonists & inhibitors
  • Cytokine Receptor Common beta Subunit / deficiency
  • Cytokine Receptor Common beta Subunit / genetics
  • Cytokine Receptor Common beta Subunit / physiology*
  • Dendritic Cells / classification
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Endotoxemia / immunology
  • Gene Expression Profiling
  • Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Homeostasis
  • Inflammation / immunology*
  • Lipopolysaccharides / toxicity
  • Listeriosis / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / transplantation
  • Organ Specificity
  • Orthomyxoviridae Infections / immunology
  • Pneumococcal Infections / immunology
  • Radiation Chimera
  • Spleen / immunology
  • Tamoxifen / pharmacology

Substances

  • Cytokine Receptor Common beta Subunit
  • Lipopolysaccharides
  • lipopolysaccharide, Escherichia coli O111 B4
  • Tamoxifen
  • Granulocyte-Macrophage Colony-Stimulating Factor