Related Experiment Videos
IL-10 production by adult human derived microglial cells
K Williams1, N Dooley, E Ulvestad
1Department of Pathology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Abstract:
Microglia, a population of central nervous system (CNS) macrophages, have been demonstrated to support immune accessory and effector functions in the CNS. Numerous studies support the role of microglia in CNS development and pathology, where activation of microglia is consistently noted. The current study investigated microglial immune functions under basal and activation conditions and assessed the ability of interleukin-10 (IL-10), added exogenously or produced by microglia, to down-regulate microglial functions. This report demonstrates that microglia from the adult human brain produce IL-10 following interferon-gamma/lipopolysaccharide activation. Functionally, recombinant human IL-10 down-regulated basal HLA-DR expression by microglia and inhibited, in a dose-dependent response, the ability of microglia to stimulate CD4+ T-cells in antigen presentation assays. These data, together with recent observations of the inhibition of experimental allergic encephalomyelitis (EAE) following IL-10 administration and reduced CNS infection by Listeria monocytogenes after anti-IL-10 treatment, suggest that IL-10 production by microglia may have important immune-regulatory functions in CNS disease and disease models.
Insights
Interleukin-10 (IL-10) produced by human microglia can regulate immune responses in the central nervous system (CNS). This cytokine inhibits microglial immune functions and T-cell stimulation, suggesting a role in CNS diseases.
Area of Science:
- Neuroimmunology
- Central Nervous System (CNS) Immunity
- Innate Immune Cells
Background:
- Microglia are CNS macrophages crucial for immune functions, development, and pathology.
- Microglial activation is a consistent feature in CNS disorders.
- The role of IL-10 in modulating microglial activity requires further investigation.
Purpose of the Study:
- To investigate microglial immune functions under basal and activated conditions.
- To assess the regulatory capacity of IL-10 on microglial functions.
- To determine if microglia produce IL-10 and if it impacts their immune accessory functions.
Main Methods:
- Activation of adult human microglia using interferon-gamma/lipopolysaccharide.
- Quantification of IL-10 production by activated microglia.
- Assessment of recombinant human IL-10's effect on HLA-DR expression.
- Evaluation of IL-10's impact on microglial antigen presentation to CD4+ T-cells.
Main Results:
- Adult human microglia produce IL-10 upon activation.
- Exogenous IL-10 down-regulated basal HLA-DR expression on microglia.
- IL-10 dose-dependently inhibited microglial stimulation of CD4+ T-cells.
- Microglia-derived IL-10 demonstrated immune-regulatory potential.
Conclusions:
- Microglia are a source of IL-10 in the human CNS.
- IL-10 produced by microglia plays a significant role in immune regulation within the CNS.
- These findings suggest IL-10's involvement in CNS diseases and their models.