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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Auteurs principaux:	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
Format:	article
Langue:	EN
Publié:	eLife Sciences Publications Ltd 2021
Sujets:	microglia spinal cord pain CSF1 meninges Treg Medicine R Science Q Biology (General) QH301-705.5
Accès en ligne:	https://doaj.org/article/62a134c3d95e44b3af89fbe8fc850844
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spelling	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)
institution	DOAJ
collection	DOAJ
language	EN
topic	microglia spinal cord pain CSF1 meninges Treg Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	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
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Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice

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