Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice
- University of California San Francisco, United States
- University of California, San Francisco, United States
- University California San Francisco, United States
Abstract
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.
Data availability
RNA sequencing data are available through GEO accession #GSE 184801All data generated or analysed during this study and required for conclusions to be drawn are included in the manuscript and supporting files.The upload can be identified at the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184801
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Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female miceNCBI Gene Expression Omnibus, GSE184801.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R35 NS097306)
- Allan Basbaum
Open Philathropy
- Allan Basbaum
Pew Charitable Trusts
- Anna Molofsky
National Institute of Mental Health (R01MH119349)
- Anna Molofsky
National Institute of Mental Health (DP2MH116507)
- Anna Molofsky
Burroughs Wellcome Fund
- Anna Molofsky
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: As noted in the description of the mice used in this study:"All mouse experiments were approved by UCSF Institutional Animal Care and Use Committee and conducted in accordance with the guidelines established by the Institutional Animal Care and Use Committee and Laboratory Animal Resource Center."Please note that this is a renewal that occurred during the course of the revision to the manuscript.APPROVAL NUMBER: AN183265-02DApproval Date: June 15, 2021Expiration Date: February 26, 2022
Copyright
© 2021, Kuhn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice
eLife 10:e69056.
https://doi.org/10.7554/eLife.69056
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