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NK and ILC1 Cells Regulate Mouse Anxiety and Memory via IF-γ and Acetylcholine

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Summary

Researchers explored how the brain communicates with immune cells, focusing on the dura layer of adult mice brains. They discovered that resident natural killer cells and innate lymphoid cells in this region play a crucial role. Specifically, they found that interferon-γ and acetylcholine, secreted by these cells, significantly influence brain activities. Interferon-γ affects the formation of non-spatial memory and alters GABAergic neurotransmission in cortical neurons, while acetylcholine helps regulate circuits associated with anxiety-like behaviors. These insights reveal new aspects of the immune system's impact on brain function, highlighting complex immune-to-brain communication pathways.

Research Criteria

This article delves into how natural killer cells and type 1 innate lymphoid cells impact cognitive and emotional processes in mice, specifically exploring their influence on anxiety and memory. It examines the way these cells modulate brain activity and behavioral responses by secreting substances like interferon-gamma and acetylcholine, highlighting the intricate connection between the immune system and neurological functions.

Sample Type

CD3−/NK1.1+ cells sorted from the meninges and spleen of C57BL/6 mice.

Result— Transcriptional Landscape of Meningeal Resident Natural Killer and Innate Lymphoid Cells 1

Exploring the transcriptional landscape of meningeal-resident NK cells and ILC1, researchers used single-cell RNA-sequencing to identify distinct clusters of these cells in adult male mice. The study highlighted unique expression patterns of chemokine receptors and adhesion molecules in meningeal and splenic NK cells/ILC1, indicating different homing mechanisms. Meningeal NK cells and ILC1 express Cxcr4, with Cxcr6 being specific to ILC1. Conversely, both cell types in the spleen express Ccr2, Ccr5, and S1pr5. Additionally, meningeal ILC1/NK cells exclusively express Smad7, Vegfa, and Ifn-g, and exhibit differences in transcription factors: Irf8 and Eomes in NK cells, and Rora in ILC1. These variations might stem from different tissue origins, innate lymphocyte plasticity, or distinct functions of meningeal cells compared to peripheral cells, suggesting avenues for further research.

The transcriptome of meningeal NK cells and ILC1. (Garofalo, 2023)Fig.1 The transcriptome of meningeal NK cells and ILC11.

Result—NK Cells and Ilc1 Regulate Cortical GABAergic Activity via Interferon Gamma Influencing Memory

Meningeal NK cells and ILC1, through interferon-gamma (IFN-γ), play a crucial role in memory regulation by influencing GABAergic activity in the prefrontal cortex (PFC). Unlike their splenic counterparts, these meningeal cells upregulate genes related to IFN-γ pathways. This modulation of IFN-γ affects memory formation, as evidenced by changes in inhibitory post-synaptic currents in PFC neurons and alterations in non-spatial memory during behavioral tests following IFN-γ depletion. The findings underscore the significant impact of meningeal immune cells on cognitive functions, revealing a direct connection between the immune system and brain activity in memory regulation.

ILC1-derived NK cell-IFN- controls non-spatial memory. (Garofalo, 2023)Fig.2 ILC1-derived NK cell-IFN- controls non-spatial memory1.

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RNA structure. (Creative Biolabs Original)

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At Creative Biolabs, we're acutely aware of the intricate variances in cellular groups. Our skill set is deeply rooted in unraveling these nuances using single-cell RNA sequencing. We expertly sift through the array of transcriptomic environments found in different cellular specimens. From the first step of sample preparation to in-depth data examination, our offerings are comprehensive, ensuring quick, adaptable, and precise outcomes for your scientific inquiries.

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At Creative Biolabs, our commitment lies in delivering exceptional single-cell RNA sequencing solutions, tailored to the unique requirements of each research project. Our proficient team, armed with advanced tools, specializes in unearthing the intricate genetic variations at a cellular level. We take pride in our ability to adapt our methodologies to fit both the scientific and budgetary needs of our clients. This approach has positioned us as a preferred partner in propelling scientific discoveries and fostering groundbreaking advancements.

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Reference

  1. Garofalo, Stefano, et al. "Natural killer cells and innate lymphoid cells 1 tune anxiety-like behavior and memory in mice via interferon-γ and acetylcholine." Nature Communications 14.1 (2023): 3103.
! ! For Research Use Only. Not for diagnostic or therapeutic purposes.

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