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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Autores principales: 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
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Publicado: eLife Sciences Publications Ltd 2021
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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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