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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

This summary is machine-generated.

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.

Keywords:

Pain enkephalin meninges neuroimmunology opioid regulatory T cells sensory neurons sex dimorphism

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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.