Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice

eLife

Veronica Craik¹  Julia A Kuhn¹  Katherine Hamel¹  Mollie Bernstein¹  Joao Braz¹  Allan I Basbaum¹  Jorge Ortiz-Carpena²  Ari B Molofsky²  Madelene W Dahlgren²  Ilia D Vainchtein³  Anna V Molofsky³ 

[1] Department of Anatomy, University of California San Francisco, San Francisco, United States;Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States;Department of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States;

关键词: microglia;    spinal cord;    pain;    CSF1;    meninges;    Treg;    Mouse;   

DOI  :  10.7554/eLife.69056

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Peripheral nerve injury-induced neuropathic pain is a chronic and debilitating condition characterized by mechanical hypersensitivity. We previously identified microglial activation via release of colony-stimulating factor 1 (CSF1) from injured sensory neurons as a mechanism contributing to nerve injury-induced pain. Here, we show that intrathecal administration of CSF1, even in the absence of injury, is sufficient to induce pain behavior, but only in male mice. Transcriptional profiling and morphologic analyses after intrathecal CSF1 showed robust immune activation in male but not female microglia. CSF1 also induced marked expansion of lymphocytes within the spinal cord meninges, with preferential expansion of regulatory T-cells (Tregs) in female mice. Consistent with the hypothesis that Tregs actively suppress microglial activation in females, Treg deficient (Foxp3DTR) female mice showed increased CSF1-induced microglial activation and pain hypersensitivity equivalent to males. We conclude that sexual dimorphism in the contribution of microglia to pain results from Treg-mediated suppression of microglial activation and pain hypersensitivity in female mice.

【 授权许可】

CC BY