Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice
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 in...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:62a134c3d95e44b3af89fbe8fc8508442021-12-02T15:31:51ZRegulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice10.7554/eLife.690562050-084Xe69056https://doaj.org/article/62a134c3d95e44b3af89fbe8fc8508442021-10-01T00:00:00Zhttps://elifesciences.org/articles/69056https://doaj.org/toc/2050-084XPeripheral 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.Julia A KuhnIlia D VainchteinJoao BrazKatherine HamelMollie BernsteinVeronica CraikMadelene W DahlgrenJorge Ortiz-CarpenaAri B MolofskyAnna V MolofskyAllan I BasbaumeLife Sciences Publications Ltdarticlemicrogliaspinal cordpainCSF1meningesTregMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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microglia spinal cord pain CSF1 meninges Treg Medicine R Science Q Biology (General) QH301-705.5 |
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microglia spinal cord pain CSF1 meninges Treg Medicine R Science Q Biology (General) QH301-705.5 Julia A Kuhn Ilia D Vainchtein Joao Braz Katherine Hamel Mollie Bernstein Veronica Craik Madelene W Dahlgren Jorge Ortiz-Carpena Ari B Molofsky Anna V Molofsky Allan I Basbaum Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
description |
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. |
format |
article |
author |
Julia A Kuhn Ilia D Vainchtein Joao Braz Katherine Hamel Mollie Bernstein Veronica Craik Madelene W Dahlgren Jorge Ortiz-Carpena Ari B Molofsky Anna V Molofsky Allan I Basbaum |
author_facet |
Julia A Kuhn Ilia D Vainchtein Joao Braz Katherine Hamel Mollie Bernstein Veronica Craik Madelene W Dahlgren Jorge Ortiz-Carpena Ari B Molofsky Anna V Molofsky Allan I Basbaum |
author_sort |
Julia A Kuhn |
title |
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
title_short |
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
title_full |
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
title_fullStr |
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
title_full_unstemmed |
Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice |
title_sort |
regulatory t-cells inhibit microglia-induced pain hypersensitivity in female mice |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/62a134c3d95e44b3af89fbe8fc850844 |
work_keys_str_mv |
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