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Astrocyte galectin-9 potentiates microglial TNF secretion.

Andrew J Steelman, Jianrong Li1

  • 1Department of Veterinary Integrative Biosciences and Institute for Neuroscience, Texas A&M University, Mail Stop 4458, College Station 77843, TX, USA. jrli@cvm.tamu.edu.

Journal of Neuroinflammation
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Galectin-9, a signaling molecule, promotes microglial activation and cytokine production. This occurs independently of T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3), suggesting a novel neuroinflammatory pathway.

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Aberrant neuroinflammation is implicated in neurological disease pathogenesis.
  • The T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3)/galectin-9 pathway is investigated for its role in innate immune cell activation.
  • Understanding glial activation pathways is crucial for neurological disease research.

Purpose of the Study:

  • To investigate the role of the Tim-3/galectin-9 pathway in glial activation in vitro.
  • To determine how galectin-9 influences microglial and astrocyte responses.
  • To elucidate the communication mechanisms between glial cells in neuroinflammation.

Main Methods:

  • Primary glial cultures (microglia, astrocytes, oligodendrocytes) were stimulated with poly(I:C) or LPS.
  • Galectin-9 expression and its effect on microglial activation were assessed using wild-type and Lgals9 null mice.
  • Tim-3's necessity in signal transduction was evaluated using neutralizing antibodies and recombinant soluble Tim-3.

Main Results:

  • Astrocytes enhanced microglial TNF production upon TLR stimulation.
  • Poly(I:C) increased galectin-9 expression in microglia; astrocyte-derived galectin-9 enhanced microglial TNF production.
  • Recombinant galectin-9 boosted poly(I:C)-induced microglial TNF and IL-6 production, independent of Tim-3.

Conclusions:

  • Galectin-9 acts as an astrocyte-microglia communication signal, promoting microglial cytokine production independently of Tim-3.
  • The Tim-3/galectin-9 pathway modulates neuroinflammatory processes.
  • CNS galectin-9 activation influences cytokine production (TNF, IL-6), potentially impacting neurological disease pathology or repair.