DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain

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.Grant sponsor: Fondo de Investigaciones Sanitarias (FIS) Spain; Grant numbers: PI09/0218 and PI12/0238; Grant sponsor: Red Tematica Investigacion Cooperativa en Cancer (RTICC); Grant number: RD12/0036/0027 We thank David Hume (The Roslin Institute, University of Edinburgh) for providing the c-fms/Csf1r EGFP mice. Batf-32/2 was kindly provided by Dr. Kenneth M. Murphy, Washington University, St. Louis, MO, USA. We thank Amanda Sierra (Universidad del Pais Vasco) for her scientific discussions. Simon Bartlett (CNIC) provided English editing