Regulatory T cell-derived enkephalin imparts pregnancy-induced analgesia.

Autor:	Midavaine É; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Moraes BC; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Benitez J; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Rodriguez SR; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Braz JM; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Kochhar NP; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Eckalbar WL; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Domingos AI; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Pintar JE; Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA., Basbaum AI; Department of Anatomy, University of California San Francisco, San Francisco, California, USA., Kashem SW; Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.; Dermatology, Veterans Affairs Medical Center, San Francisco, California, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 14. Date of Electronic Publication: 2024 May 14.
DOI:	10.1101/2024.05.11.593442
Abstrakt:	T cells have emerged as sex-dependent orchestrators of pain chronification but the sexually dimorphic mechanisms by which T cells control pain sensitivity is not resolved. Here, we demonstrate an influence of regulatory T cells (Tregs) on pain processing that is distinct from their canonical functions of immune regulation and tissue repair. Specifically, meningeal Tregs (mTregs) express the endogenous opioid, enkephalin, and mTreg-derived enkephalin exerts an antinociceptive action through a presynaptic opioid receptor signaling mechanism that is dispensable for immunosuppression. mTregs are both necessary and sufficient for suppressing mechanical pain sensitivity in female but not male mice. Notably, the mTreg modulation of pain thresholds depends on sex-hormones and expansion of enkephalinergic mTregs during gestation imparts a remarkable pregnancy-induced analgesia in a pre-existing, chronic, unremitting neuropathic pain model. These results uncover a fundamental sex-specific, pregnancy-pronounced, and immunologically-derived endogenous opioid circuit for nociceptive regulation with critical implications for pain biology and maternal health. Competing Interests: Disclosures: Authors have no conflicts of interests to declare.
Databáze:	MEDLINE
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