Meningeal regulatory T cells inhibit nociception in female mice

作者：Élora Midavaine, Beatriz Caroline de Moraes, Jorge Benitez, Sian Rodriguez-Rosado, João M. Bráz, Nathan P. Kochhar, Walter L. Eckalbar, Lin Tian, Ana Isabel Domingos, John E. Pintar, Allan I. Basbaum, Sakeen W. Kashem · 发表于：Science · 年份：2025 · DOI：10.1126/science.adq6531 · 被引用次数：43 · 研究领域：Pain Mechanisms and Treatments、Neuropeptides and Animal Physiology、Neuroinflammation and Neurodegeneration Mechanisms

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 (T reg 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 T reg cells (mT reg cells) in mice led to female-specific and sex hormone–dependent modulation of mechanical sensitivity. Specifically, mT reg 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 T reg cell–mediated immunosuppression. Thus, our findings uncovered a sexually dimorphic immunological circuit that restrains nociception, establishing T reg cells as sentinels of pain homeostasis.