title: Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.
abstract: Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5-7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Niroshana
authors.initials: N
authors.lastname: Anandasabapathy
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Victora
authors.forename: Matthew
authors.initials: M
authors.lastname: Meredith
authors.forename: Rachel
authors.initials: R
authors.lastname: Feder
authors.forename: Baojun
authors.initials: B
authors.lastname: Dong
authors.forename: Courtney
authors.initials: C
authors.lastname: Kluger
authors.forename: Kaihui
authors.initials: K
authors.lastname: Yao
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002831:Choroid Plexus / Q000166:cytology*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006207:Half-Life; D008578:Meninges / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D017628:Microglia / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
chemical_list: D051192:Receptors, Pattern Recognition; D014157:Transcription Factors; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3