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Related Concept Videos

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Extracellular microRNAs modulate human microglial function through TLR8.

Hannah Weidling1,2,3, Edyta Motta1,2, Leonard D Kuhrt2,3,4

  • 1Institute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Frontiers in Immunology
|December 1, 2025
PubMed
Summary
This summary is machine-generated.

Central nervous system (CNS) disease-associated microRNAs (miRNAs) signal through Toll-like receptor 8 (TLR8) to regulate human microglia function. These miRNAs modulate neuroinflammation and neurite outgrowth, offering potential therapeutic targets for CNS diseases.

Keywords:
Alzheimer's diseaseextracellular microRNAgliomahuman microgliaiPSCmicroglial functionstem cellstoll-like receptor 8

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Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • MicroRNAs (miRNAs) are key gene regulators in the brain, with dysregulation implicated in central nervous system (CNS) diseases.
  • MicroRNAs can act as ligands for Toll-like receptors (TLRs), influencing immune responses.

Purpose of the Study:

  • To investigate CNS disease-associated miRNAs as signaling molecules for human microglia.
  • To determine the role of Toll-like receptors (TLRs) in mediating miRNA effects on microglia.

Main Methods:

  • Machine learning identified Alzheimer's disease (AD) and glioma-associated miRNAs as TLR7/TLR8 ligands.
  • Human microglia-like cells (iMGLs) were used to assess miRNA-induced changes in cytokine release, motility, and phagocytosis.
  • A selective TLR8 antagonist (CU-CPT9a) was employed to confirm receptor involvement.

Main Results:

  • Specific miRNAs (miR-9-5p, miR-132-5p, etc.) were identified as ligands for TLR7 and TLR8.
  • Exposure to certain miRNAs modulated iMGL cytokine production (IL-6, TNF), motility, and phagocytosis.
  • TLR8 antagonism abolished miRNA-induced microglial responses, and extracellular miRNAs reduced neurite length in co-cultures.

Conclusions:

  • CNS disease-associated miRNAs function as signaling molecules for human microglia via TLR8.
  • These miRNAs regulate microglial functions and neuroinflammatory responses, impacting neurite outgrowth.