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Regulatory T cell-derived enkephalin gates nociception.
Élora Midavaine1, Beatriz C Moraes1, Jorge Benitez1
1Department of Anatomy, University of California San Francisco, San Francisco, California, USA.
Biorxiv : the Preprint Server for Biology
|May 27, 2024
Summary
Regulatory T cells (Tregs) in the meninges express enkephalin, an endogenous opioid. This mechanism suppresses pain in female mice, highlighting a sex-specific, immune-derived pain regulation pathway.
Area of Science:
- Neuroimmunology
- Pain research
- Sex differences in biology
Background:
- T cells are implicated in chronic pain, but sex-specific mechanisms remain unclear.
- Regulatory T cells (Tregs) typically regulate immune responses and tissue repair.
- The role of meningeal Tregs (mTregs) in pain processing is not well understood.
Purpose of the Study:
- To investigate the role of meningeal Tregs (mTregs) in pain processing.
- To elucidate the mechanisms by which mTregs influence pain sensitivity.
- To determine if these mechanisms are sex-dependent.
Main Methods:
- Investigated Treg function in mouse models of pain.
- Analyzed enkephalin expression in mTregs.
- Examined opioid receptor signaling pathways.
- Assessed pain sensitivity in male and female mice under varying hormonal conditions.
Main Results:
- Meningeal Tregs (mTregs) express the endogenous opioid enkephalin.
- mTreg-derived enkephalin mediates antinociception via presynaptic opioid receptors.
- This pain suppression is observed in female mice but not male mice.
- The observed sex-specific effect is dependent on sex hormones.
Conclusions:
- Meningeal Tregs (mTregs) possess a novel, non-immunosuppressive function in pain modulation.
- An immunologically-derived, sex-specific endogenous opioid circuit regulates nociception.
- This pathway, dependent on sex hormones, offers critical insights into pain biology and sex dimorphism.
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