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Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Single-cell analysis of CD14+CD16+ monocytes identifies a subpopulation with an enhanced migratory and inflammatory
Vanessa Y Ruiz1, Tina M Calderon1, Rosiris Leon-Rivera1
1Department of Pathology, Albert Einstein College of Medicine, New York, NY, United States.
Abstract:
Monocytes in the central nervous system (CNS) play a pivotal role in surveillance and homeostasis, and can exacerbate pathogenic processes during injury, infection, or inflammation. CD14+CD16+ monocytes exhibit diverse functions and contribute to neuroinflammatory diseases, including HIV-associated neurocognitive impairment (HIV-NCI). Analysis of human CD14+CD16+ monocytes matured in vitro by single-cell RNA sequencing identified a heterogenous population of nine clusters. Ingenuity pathway analysis of differentially expressed genes in each cluster identified increased migratory and inflammatory pathways for a group of clusters, which we termed Group 1 monocytes. Group 1 monocytes, distinguished by increased ALCAM, CD52, CD63, and SDC2, exhibited gene expression signatures implicated in CNS inflammatory diseases, produced higher levels of CXCL12, IL-1Ra, IL-6, IL-10, TNFα, and ROS, and preferentially transmigrated across a human in vitro blood-brain barrier model. Thus, Group 1 cells within the CD14+CD16+ monocyte subset are likely to be major contributors to neuroinflammatory diseases.
Insights
Researchers identified a specific monocyte subset (Group 1 CD14+CD16+ monocytes) that significantly contributes to neuroinflammation and central nervous system (CNS) diseases. These monocytes show increased migratory and inflammatory markers, exacerbating conditions like HIV-associated neurocognitive impairment.
Area of Science:
- Neuroimmunology
- Single-cell genomics
- Central Nervous System (CNS) research
Background:
- Monocytes are crucial for CNS surveillance but can worsen neuroinflammation during injury or infection.
- CD14+CD16+ monocytes have diverse roles and are implicated in neuroinflammatory diseases such as HIV-associated neurocognitive impairment (HIV-NCI).
Purpose of the Study:
- To analyze the heterogeneity of human CD14+CD16+ monocytes.
- To identify specific monocyte subsets that contribute to neuroinflammation and CNS diseases.
Main Methods:
- Single-cell RNA sequencing of in vitro-matured human CD14+CD16+ monocytes.
- Ingenuity pathway analysis to identify differentially expressed genes and pathways.
- In vitro blood-brain barrier transmigration assays.
Main Results:
- Identified nine distinct clusters within CD14+CD16+ monocytes.
- A subset, termed Group 1 monocytes, exhibited increased migratory and inflammatory gene expression (ALCAM, CD52, CD63, SDC2).
- Group 1 monocytes produced higher levels of inflammatory cytokines (CXCL12, IL-1Ra, IL-6, IL-10, TNFα) and reactive oxygen species (ROS), and showed preferential transmigration across an in vitro blood-brain barrier.
Conclusions:
- Group 1 monocytes represent a key subset of CD14+CD16+ monocytes driving neuroinflammation.
- These findings highlight Group 1 monocytes as significant contributors to the pathogenesis of CNS inflammatory diseases.
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