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.

A case of mistaken identity: CD11c‐eYFP+ cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells

“…Consistent with Bulloch et al (2008), CD11c-eYFP 1 cells were also distributed in regions of neurogenesis, such as the subventricular zones of the lateral ventricles, and throughout the rostral migratory stream. Microglia within the subgranular zone of the hippocampus and subventricular zone of the lateral ventricles regulate neurogenesis via the secretion of neurotrophic factors, fractalkine/CX3CR1 signalling and phagocytosis of apoptotic cells (Sato, 2015 (Chinnery et al, 2010;McMenamin, 1999;Quintana et al, 2015). Meningeal/choroid plexus DCs significantly expand in numbers following Flt3 treatment and have a similar transcriptional profile to CD8 1 spleen DCs.…”

“…CD11c-eYFP 1 cells from the choroid plexus and pia mater expressed mature DC and macrophage markers, and were phenotypically distinct from those within the parenchyma of the cerebral cortex. It has been well established that the choroid plexus and meninges are a rich source of macrophages and DCs (Chinnery et al, 2010;McMenamin, 1999;Quintana et al, 2015). Meningeal/choroid plexus DCs significantly expand in numbers following Flt3 treatment and have a similar transcriptional profile to CD8 1 spleen DCs.…”

Infectious immunity in the central nervous system and brain function

“…These signs are the result of catecholamine expression by phagocytes exposed to bacterial products 29 , which promotes mydriasis, leading to excessive transfer of light to the brain and vasospasm 30 . Antigen-presenting cells (APCs) that reside within the choroid plexus and meninges express major histocompatibility complex class II and the C-type lectin receptor DNGR-1, also known as CLEC9A 31 , a marker of dendritic cell subsets with functional similarity to lymphoid and tissue dendritic cells. These resident APCs provide a mechanism for local restimulation of infiltrating T cells, which is required for their extravasation into the CNS parenchyma 32,33 .…”

Myeloid Cells in the Central Nervous System

“…It is home to its own tissue-resident macrophage, the epiplexus cell, as well as to monocytes, dendritic cells (DCs), and mast cells (Allen, 1975; Kappers et al, 1958; Quintana et al, 2015; Shechter et al, 2013a). The choroid plexus has been viewed as an “educative gate” that skews immune cells towards a more anti-inflammatory phenotype.…”