Fins-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain

James F. Curtin, Gwendalyn D. King, Carlos Barcia, Chunyan Liu, François X. Hubert, Carole Guillonneau, Régis Josien, Ignacio Anegon, Pedro E. Lowenstein, Maria G. Castro

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The lack of professional afferent APCs in naive brain parenchyma contributes to the systemic immune ignorance to Ags localized exclusively within the brain. Dendritic cells (DCs) appear within the brain as a consequence of inflammation, but no molecular mechanisms accounting for this influx have been described. In this study we demonstrate that Fms-like tyrosine kinase 3 ligand (Flt3) recruits plasmacytoid DCs (pDCs; >50-fold; p < 0.001) to the brain parenchyma. These pDCs expressed IFN-α, the hallmark cytokine produced by pDCs, indicating recruitment and activation in situ of bona fide pDCs within the brain parenchyma. Flt3L did not increase the numbers of conventional DCs, macrophages, or B, T, NK, NKT, or microglial cells within the brain. Our data demonstrate that FltL reconstitutes a crucial afferent component of the immune response, namely, professional APCs within the brain parenchyma, and this could counteract the intrinsic systemic immune ignorance to Ags localized exclusively within the brain.

Original languageEnglish (US)
Pages (from-to)3566-3577
Number of pages12
JournalJournal of Immunology
Volume176
Issue number6
DOIs
StatePublished - Mar 15 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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