title: DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain.
abstract: The role and different origin of brain myeloid cells in the brain is central to understanding how the central nervous system (CNS) responds to injury. C-type lectin receptor family 9, member A (DNGR-1/CLEC9A) is a marker of specific DC subsets that share functional similarities, such as CD8α(+) DCs in lymphoid tissues and CD103(+) CD11b(low) DCs in peripheral tissues. Here, we analyzed the presence of DNGR-1 in DCs present in the mouse brain (bDCs). Dngr-1/Clec9a mRNA is expressed mainly in the meningeal membranes and choroid plexus (m/Ch), and its expression is enhanced by fms-like tyrosine kinase 3 ligand (Flt3L), a cytokine involved in DC homeostasis. Using Clec9a(egfp/egfp) mice, we show that Flt3L induces accumulation of DNGR-1-EGFP(+) cells in the brain m/Ch. Most of these cells also express major histocompatibility complex class II (MHCII) molecules. We also observed an increase in specific markers of cDC CD8α+ cells such as Batf-3 and Irf-8, but not of costimulatory molecules such as Cd80 and Cd86, indicating an immature phenotype for these bDCs in the noninjured brain. The presence of DNGR-1 in the brain provides a potential marker for the study of this specific brain cell subset. Knowledge and targeting of brain antigen presenting cells (APCs) has implications for the fight against brain diseases such as neuroinflammation-based neurodegenerative diseases, microbe-induced encephalitis, and brain tumors such as gliomas.
authors.affiliation: Neuroinflammation Unit. Unidad Funcional De Investigación De Enfermedades Crónicas, Instituto De Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Quintana
authors.affiliation: Neuroinflammation Unit. Unidad Funcional De Investigación De Enfermedades Crónicas, Instituto De Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Neuroinflammation Unit. Unidad Funcional De Investigación De Enfermedades Crónicas, Instituto De Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Velasco
authors.affiliation: Department of Immunology, Centro Nacional De Microbiología, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de Andrés
authors.affiliation: Instituto De Salud Carlos III, Neural Regeneration Unit. Unidad Funcional De Investigación De Enfermedades Crónicas, Majadahonda, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Liste
authors.affiliation: Centro Nacional De Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sancho
authors.affiliation: Department of Immunology, Centro Nacional De Microbiología, Instituto De Salud Carlos III, Madrid, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Gaspar
authors.affiliation: Neuroinflammation Unit. Unidad Funcional De Investigación De Enfermedades Crónicas, Instituto De Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Cano
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002831:Choroid Plexus / Q000166:cytology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005802:Genes, MHC Class II / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008578:Meninges / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D049452:Green Fluorescent Proteins; D050835:Interferon Regulatory Factors; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C529914:Clec9a protein, mouse; C533289:SNFT protein, mouse; C485184:enhanced green fluorescent protein; C084881:flt3 ligand protein; C516770:Ptprc protein, mouse
keywords: Batf3; C-type lectin receptors; CD11c; Flt3L; myeloid cells; neuroinflammation