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

Melanie Greter, Julie Helft, Andrew Chow, Daigo Hashimoto, Arthur Mortha, Judith Agudo-Cantero, Milena Bogunovic, Emmanuel L Gautier, Jennifer Miller, Marylene Leboeuf, Geming Lu, Costica Aloman, Brian D Brown, Jeffrey W Pollard, Huabao Xiong, Gwendalyn J Randolph, Jerry E Chipuk, Paul S Frenette, Miriam Merad

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1031-1046
Number of pages16
JournalImmunity
Volume36
Issue number6
DOIs
Publication statusPublished - 29 Jun 2012

Keywords

  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Lineage
  • Cytokine Receptor Common beta Subunit
  • Dendritic Cells
  • Encephalomyelitis, Autoimmune, Experimental
  • Endotoxemia
  • Gene Expression Profiling
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Homeostasis
  • Inflammation
  • Lipopolysaccharides
  • Listeriosis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes
  • Organ Specificity
  • Orthomyxoviridae Infections
  • Pneumococcal Infections
  • Radiation Chimera
  • Spleen
  • Tamoxifen

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