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Elife. 2021 Oct 15;10. doi: 10.7554/eLife.69056.

Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice.

eLife

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

Affiliations

  1. Department of Anatomy, University of California San Francisco, San Francisco, United States.
  2. Department of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States.
  3. Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States.

PMID: 34652270 PMCID: PMC8639143 DOI: 10.7554/eLife.69056

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 (

© 2021, Kuhn et al.

Keywords: CSF1; Treg; meninges; microglia; mouse; neuroscience; pain; spinal cord

Conflict of interest statement

JK Patent approved on use of CSF1 blockade to treat neuropathic pain (Publication Number WO/2016/057800). IV, JB, KH, MB, VC, MD, JO, AM, AM No competing interests declared, AB Reviewing editor, eLife

References

  1. Bioinformatics. 2015 Jan 15;31(2):166-9 - PubMed
  2. Pain. 2019 Feb;160(2):358-366 - PubMed
  3. J Neurosci. 2012 Aug 15;32(33):11330-42 - PubMed
  4. Cell Res. 2014 Nov;24(11):1374-7 - PubMed
  5. Nat Methods. 2012 Jun 28;9(7):676-82 - PubMed
  6. Nature. 2021 Feb;590(7846):473-479 - PubMed
  7. Nat Immunol. 2007 Feb;8(2):191-7 - PubMed
  8. Eur J Pain. 2018 Nov;22(10):1735-1756 - PubMed
  9. Nat Methods. 2014 Oct;11(10):982-4 - PubMed
  10. Cell. 2017 Jun 15;169(7):1276-1290.e17 - PubMed
  11. Trends Mol Med. 2019 Sep;25(9):741-749 - PubMed
  12. Pharmacol Res. 2019 Jan;139:1-16 - PubMed
  13. Nat Neurosci. 2015 Aug;18(8):1081-3 - PubMed
  14. Cell Rep. 2018 Sep 4;24(10):2773-2783.e6 - PubMed
  15. Bone. 2012 Jan;50(1):42-53 - PubMed
  16. J Pain. 2003 Oct;4(8):465-70 - PubMed
  17. Nat Biotechnol. 2010 May;28(5):511-5 - PubMed
  18. Genome Biol. 2014;15(12):550 - PubMed
  19. Nat Rev Neurosci. 2020 Jul;21(7):353-365 - PubMed
  20. Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17045-17050 - PubMed
  21. Dev Neurobiol. 2018 Jun;78(6):618-626 - PubMed
  22. J Neurosci. 2009 Nov 18;29(46):14415-22 - PubMed
  23. Bioinformatics. 2019 Jun 1;35(12):2084-2092 - PubMed
  24. Brain Behav Immun. 2018 May;70:157-165 - PubMed
  25. Nucleic Acids Res. 2015 Apr 20;43(7):e47 - PubMed
  26. Proc Natl Acad Sci U S A. 2019 May 14;116(20):9969-9978 - PubMed
  27. Cell. 2020 Aug 6;182(3):625-640.e24 - PubMed
  28. Annu Rev Cell Dev Biol. 2018 Oct 6;34:523-544 - PubMed
  29. Mol Pain. 2011 Sep 11;7:66 - PubMed
  30. Br J Anaesth. 1999 Aug;83(2):235-40 - PubMed
  31. Cell. 2008 May 30;133(5):775-87 - PubMed
  32. Nat Commun. 2020 Jan 14;11(1):264 - PubMed
  33. PLoS Biol. 2021 Mar 19;19(3):e3001154 - PubMed
  34. Science. 2019 Jul 5;365(6448):32-33 - PubMed
  35. Bioinformatics. 2016 Sep 15;32(18):2847-9 - PubMed
  36. PLoS One. 2016 Apr 12;11(4):e0153375 - PubMed
  37. Cell Rep. 2018 Jan 16;22(3):832-847 - PubMed
  38. J Neurosci. 2016 Jul 13;36(28):7353-63 - PubMed
  39. Trends Neurosci. 2020 Mar;43(3):144-154 - PubMed
  40. Pain. 2021 Sep 1;162(9):2366-2375 - PubMed
  41. Pain. 2020 Aug;161(8):1730-1743 - PubMed
  42. Mol Pain. 2009 Mar 27;5:16 - PubMed
  43. Cell. 2019 Feb 7;176(4):716-728.e18 - PubMed
  44. J Neurosci. 2011 Oct 26;31(43):15450-4 - PubMed
  45. Sci Immunol. 2019 Oct 11;4(40): - PubMed
  46. Annu Rev Immunol. 2020 Apr 26;38:597-620 - PubMed
  47. Bioinformatics. 2013 Jan 1;29(1):15-21 - PubMed
  48. Exp Neurol. 2020 Jun;328:113233 - PubMed
  49. Cell Rep. 2018 Jun 19;23(12):3501-3511 - PubMed
  50. Cell. 2017 Jun 1;169(6):1119-1129.e11 - PubMed
  51. Nat Commun. 2019 Apr 3;10(1):1523 - PubMed
  52. Nat Rev Neurosci. 2018 Oct;19(10):622-635 - PubMed
  53. Nat Neurosci. 2016 Jan;19(1):94-101 - PubMed
  54. Elife. 2021 Oct 15;10: - PubMed
  55. Neuron Glia Biol. 2006 Nov;2(4):293-308 - PubMed
  56. Front Pharmacol. 2020 Jun 19;11:925 - PubMed
  57. Methods Mol Biol. 2017;1559:333-342 - PubMed
  58. Nat Commun. 2020 Apr 14;11(1):1773 - PubMed

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