Dendritic Cells

Technical advances, such as multiparameter flow cytometry and genetic tools including single-cell transcriptomics, have led to the realization that DCs are a diverse population of cells from a developmental and functional standpoint. Based on function, phenotype, and tissue distribution, DCs can be divided into two major subsets: plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). cDCs are found across lymphoid organs (thymus, spleen, and LN) and non-lymphoid organs (lung, gut, and skin). In mice, cDCs populating the lymphoid organs are subdivided into cDC1 and cDC2 cells, while the cDCs in non-lymphoid organs are subdivided into CD103⁺ and CD11b⁺ cells. Similarly, human cDCs are subdivided into CD141⁺/BDCA3⁺ and CD1c⁺/BDCA1⁺ cells in spleen and lung, CD103⁺ and CD103^- cells in the intestine, and CD14⁺ and CD14^- cells in the dermis. Besides pDCs and cDCs, there are specialized antigen presenting cells called Langerhans cells (LC), which can be found selectively in the epidermis.

Technical advances, such as multiparameter flow cytometry and genetic tools including single-cell transcriptomics, have led to the realization that DCs are a diverse population of cells from a developmental and functional standpoint. Based on function, phenotype, and tissue distribution, DCs can be divided into two major subsets: plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). cDCs are found across lymphoid organs (thymus, spleen, and LN) and non-lymphoid organs (lung, gut, and skin). In mice, cDCs populating the lymphoid organs are subdivided into cDC1 and cDC2 cells, while the cDCs in non-lymphoid organs are subdivided into CD103⁺ and CD11b⁺ cells. Similarly, human cDCs are subdivided into CD141⁺/BDCA3⁺ and CD1c⁺/BDCA1⁺ cells in spleen and lung, CD103⁺ and CD103^- cells in the intestine, and CD14⁺ and CD14^- cells in the dermis. Besides pDCs and cDCs, there is specialized antigen presenting cells called Langerhans cells (LC), which can be found selectively in the epidermis.

In the steady state, the brain contains several populations of myeloid cells located at distinct sites. Microglia cells are identified in the parenchyma, while macrophages and some dendritic cells can be found in the perivascular region, choroid plexus, and meninges. Each of these cell types is derived at a different time in ontogenesis and execute various tasks during homeostasis and surveillance. Microglia cells are derived from erythromyeloid progenitors in the yolk sac during primitive hematopoiesis happening around embryonic day 7.5-8 (E7.5-8). CNS macrophages are differentiated from different sources during embryogenesis, first in the aorta–gonad–mesonephros (AGM) region at E10.5 and then in the fetal liver (E12.5) during definitive hematopoiesis. Postnatally, the primary source of macrophages are monocytes differentiated from bone marrow HSC progenitors through subsequent differentiation stages including MDP and cMOP. DCs are also derived from MDP through subsequent differentiation of MDP to CDP and pre-cDC. 

In homeostasis, the neuro-supportive role of microglia is mediated by the secretion of trophic factors, such as BDNF (brain-derived neurotrophic factor), pruning of neuronal synapses and removal of dead cells and β-amyloid peptides. Macrophages play an essential role in the uptake of local debris and dying cells. Perivascular macrophages clear β-amyloid from CNS and maintain brain blood-barrier integrity through regulation of vascular construction. 

Under acute (e.g., ischemic stroke) or chronic inflammatory signals (e.g., Parkinson's disease or Alzheimer’s disease), microglial cells become activated and differentiate into effective APCs. The inflammatory response in the brain attracts peripheral DCs to the inflammation site for antigen uptake. Upon antigen uptake and maturation, DCs migrate to secondary lymphoid organs to present these antigens to T-cells in order to activate neuroprotective or neurodestructive pathways mediated by Tregs or Th1/Th17 cells, respectively.

HSC: Hematopoietic Stem Cell
MDP: Monocyte/DC Progenitor
CDP: Common Dendritic Cell Progenitor
Pre-cDC: Precursor of conventional/classic DC
cMOP: Common Monocyte Progenitor
DC: Dendritic Cell

Learn more about Microglia function in different diseases with our Microglia webpage.

References:

1. Prinz M., et al. 2011. Nat. Neurosci. 14:1227. PubMed
2. Prinz M. and Priller J. 2014. Nat. Rev. Neurosci. 15:300. PubMed
3. Ludewig P., et al. 2016. Biochim. Biophys. Acta. 1862:352. PubMed
4. Herz J., et al. 2017. Immunity. 46:943. PubMed

BioLegend offers a comprehensive portfolio of products to study macrophages and DCs, and interrogate their involvement in inflammatory pathways in the CNS. 

Upon pathogen encounter, DC cells undergo a process of morphological and functional changes known as maturation. This process includes:

Phenotypic changes: Up-regulation of MHC and co-stimulatory molecules and changes in the pattern of expression of adhesion molecules and chemokine receptors. 

Morphological changes: Development of dendrites and cytoskeleton reorganization. 

Functional changes: Down-regulation of antigen uptake and secretion of chemokines and cytokines. 

Upon maturation, DC cells migrate to lymphoid organs where they interact with naïve T cells to drive their activation and differentiation to cytotoxic and helper subsets.

Learn More With Webpages And Interactive Pathway Posters:
Nature Reviews Poster: Dendritic Cells: Controllers of Adaptive Immunity
Dendritic Cell, Monocyte, and Macrophage Biology Poster
Innate Immune Signaling Poster
Innate Immune Signaling Webpage
Toll-Like Receptors Webpage

References:

1. Pakalniškytė D. and Schraml B.U. 2017. Adv. Immunol. 134:89. PubMed