Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice
Kuhn, Julia A ; Vainchtein, Ilia D ; Braz, Joao ; Hamel, Katherine ; Bernstein, Mollie ; Craik, Veronica ; Dahlgren, Madelene W LU
; Ortiz-Carpena, Jorge
; Molofsky, Ari B
and Molofsky, Anna V
, et al.
(2021)
In eLife
10.
- 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... (More)
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.
(Less)
- author
- Kuhn, Julia A
; Vainchtein, Ilia D
; Braz, Joao
; Hamel, Katherine
; Bernstein, Mollie
; Craik, Veronica
; Dahlgren, Madelene W
LU
; Ortiz-Carpena, Jorge
; Molofsky, Ari B
and Molofsky, Anna V
, et al. (More)
- Kuhn, Julia A
; Vainchtein, Ilia D
; Braz, Joao
; Hamel, Katherine
; Bernstein, Mollie
; Craik, Veronica
; Dahlgren, Madelene W
LU
; Ortiz-Carpena, Jorge
; Molofsky, Ari B
; Molofsky, Anna V
and Basbaum, Allan I
(Less)
- publishing date
- 2021-10-15
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Female, Injections, Spinal, Macrophage Colony-Stimulating Factor/administration & dosage, Male, Mice, Microglia/metabolism, Neuralgia/genetics, Sex Factors, T-Lymphocytes, Regulatory/physiology
- in
- eLife
- volume
- 10
- article number
- e69056
- publisher
- eLife Sciences Publications
- external identifiers
-
- scopus:85118228783
- pmid:34652270
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.69056
- language
- English
- LU publication?
- no
- additional info
- © 2021, Kuhn et al.
- id
- 05ccabad-61b6-4ed7-b014-e51df499bba2
- date added to LUP
- 2024-05-05 23:59:15
- date last changed
- 2024-05-06 09:33:06
@article{05ccabad-61b6-4ed7-b014-e51df499bba2,
abstract = {{<p>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.</p>}},
author = {{Kuhn, Julia A and Vainchtein, Ilia D and Braz, Joao and Hamel, Katherine and Bernstein, Mollie and Craik, Veronica and Dahlgren, Madelene W and Ortiz-Carpena, Jorge and Molofsky, Ari B and Molofsky, Anna V and Basbaum, Allan I}},
issn = {{2050-084X}},
keywords = {{Animals; Female; Injections, Spinal; Macrophage Colony-Stimulating Factor/administration & dosage; Male; Mice; Microglia/metabolism; Neuralgia/genetics; Sex Factors; T-Lymphocytes, Regulatory/physiology}},
language = {{eng}},
month = {{10}},
publisher = {{eLife Sciences Publications}},
series = {{eLife}},
title = {{Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice}},
url = {{http://dx.doi.org/10.7554/eLife.69056}},
doi = {{10.7554/eLife.69056}},
volume = {{10}},
year = {{2021}},
}