Midavaine Élora, Moraes Beatriz C, Benitez Jorge, Rodriguez Sian R, Braz Joao M, Kochhar Nathan P, Eckalbar Walter L, Tian Lin, Domingos Ana I, Pintar John E, Basbaum Allan I, Kashem Sakeen W
Department of Anatomy, University of California San Francisco, San Francisco, CA, USA.
Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
Science. 2025 Apr 4;388(6742):96-104. doi: 10.1126/science.adq6531. Epub 2025 Apr 3.
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 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 cells (mT cells) in mice led to female-specific and sex hormone-dependent modulation of mechanical sensitivity. Specifically, mT 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 cell-mediated immunosuppression. Thus, our findings uncovered a sexually dimorphic immunological circuit that restrains nociception, establishing T cells as sentinels of pain homeostasis.
T细胞已成为疼痛放大的协调者，但T细胞控制疼痛处理的机制尚未明确。我们发现调节性T细胞（Treg细胞）可通过一种不依赖于其调节免疫激活和组织修复能力的机制来抑制伤害感受。小鼠脑膜T细胞（mT细胞）的位点特异性耗竭或扩增导致了机械敏感性的雌性特异性和性激素依赖性调节。具体而言，mT细胞产生内源性阿片肽脑啡肽，其通过MrgprD感觉神经元表达的δ阿片受体发挥抗伤害感受作用。虽然脑啡肽抑制伤害感受处理，但它对于Treg细胞介导的免疫抑制是可有可无的。因此，我们的研究结果揭示了一种抑制伤害感受的性别二态性免疫回路，将T细胞确立为疼痛稳态的哨兵。
