Immune cells have unexpected role in fighting pain, but only in female mice

Amazing stuff!

A case of sex discrimination in nature! I will call my attorney!😊 Just kidding!

"Unlike the combative immune cells that protect us from pathogens, regulatory T cells (Tregs) are nurturers. They salve inflammation, promote healing of injured tissue, and rein in immune attacks to curb self-inflicted damage.

Now, a study of mice ... suggests some Tregs also act on nerve cells to quell a specific type of pain—but only in females. Why only female rodents seem to benefit remains unclear, but researchers hope they might someday enlist these Tregs to address pain conditions, many of which disproportionately affect women. ..."

From the editor's summary and abstract:

"Editor’s summary

Regulatory T (Treg) cells play a well-defined role in restraining inflammatory immune responses. Midavaine et al. found that depleting Treg cells specifically localized to the meninges of the central nervous system (mTreg cells) increased the responses of female, but not male, mice to mechanical pain stimuli.

These mTreg cells were a source of enkephalin, an endogenous opioid peptide, within the cerebrospinal fluid.

In the context of nerve injury, the enkephalin associated with mTreg cells could decrease pain sensing by activating the δ-opioid receptor expressed by a subset of nociceptive neurons involved in mechanical pain sensing.

Injecting the cytokine interleukin-2 (IL-2) into the spinal fluid increased mTreg cell numbers and decreased mechanical pain sensing in female mice after nerve injury. The analgesic effect of IL-2 in female mice could be prevented by blocking female sex hormones. ...

Abstract

T cells have emerged as orchestrators of pain amplification, but the mechanism by which T cells control pain processing is unresolved.

We found that regulatory T cells (Treg cells) could inhibit nociception through a mechanism that was not dependent on their ability to regulate immune activation and tissue repair.

Site-specific depletion or expansion of meningeal Treg cells (mTreg cells) in mice led to female-specific and sex hormone–dependent modulation of mechanical sensitivity. Specifically, mTreg cells produced the endogenous opioid enkephalin that exerted an antinociceptive action through the delta opioid receptor expressed by MrgprD+ sensory neurons.

Although enkephalin restrains nociceptive processing, it was dispensable for Treg cell–mediated immunosuppression.

Thus, our findings uncovered a sexually dimorphic immunological circuit that restrains nociception, establishing Treg cells as sentinels of pain homeostasis."

Immune cells have unexpected role in fighting pain | Science | AAAS "Inflammation-suppressing regulatory T cells reduce pain in female mice by targeting nerve cells"

[I was unable to find an original news release for this discovery!]

Meningeal regulatory T cells inhibit nociception in female mice (no public access)

Regulatory T cells (pink) in membranes near the mouse spinal cord send pain-suppressing signals to nerves.