Back to Search
Start Over
Depletion of Foxp3+ regulatory T cells increases severity of mechanical allodynia and significantly alters systemic cytokine levels following peripheral nerve injury.
- Source :
-
Cytokine [Cytokine] 2015 Feb; Vol. 71 (2), pp. 207-14. Date of Electronic Publication: 2014 Nov 20. - Publication Year :
- 2015
-
Abstract
- Neuropathic pain is a debilitating condition caused by damage to the somatosensory nervous system, such as peripheral nerve injury. The immune system, and in particular the adaptive T cell response, plays a key role in mediating such pain. Regulatory T (Treg) cells are a small subpopulation of inhibitory T cells that prevent autoimmunity, limit immunopathology and maintain immune homeostasis. Here, we investigated the effects of conditional depletion of Treg cells on mechanical allodynia and serum cytokines in mice with chronic constriction injury (CCI) of the sciatic nerve, an animal model of neuropathic pain. We demonstrate that CCI induced the infiltration of small numbers of Treg cells within effected neuronal tissue. Utilising the transgenic DEREG (DEpletion of REGulatory T cells) mice, we confirmed effective depletion of Foxp3+ Treg cells by diphtheria toxin injections. Following CCI we observed a transient, though significant, increase in pain hypersensitivity for Treg-depleted DEREG mice compared to non-Treg-depleted mice. Analysis of systemic cytokine levels demonstrated significant changes in serum cytokine expression profiles. In particular, we observed significant increases in systemic concentration of RANTES, IL-2 and IL-5, and significant decreases in IL-12 and IFN-γ in nerve-injured Treg-depleted DEREG mice. Further analysis indicated a substantial increase in the serum concentration of IL-12p40 as a direct result of Treg cell depletion. These results suggest that depletion of Foxp3+ Treg cells promote nerve injury-induced pain hypersensitivity, partially by inducing altered systemic concentrations of cytokines, which may act to regulate neuropathic pain.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Blotting, Western
Chemokine CCL5 immunology
Chemokine CCL5 metabolism
Cytokines metabolism
Diphtheria Toxin toxicity
Disease Models, Animal
Flow Cytometry
Forkhead Transcription Factors immunology
Forkhead Transcription Factors metabolism
Hyperalgesia metabolism
Hyperalgesia physiopathology
Interferon-gamma immunology
Interferon-gamma metabolism
Interleukin-12 immunology
Interleukin-12 metabolism
Interleukin-2 immunology
Interleukin-2 metabolism
Interleukin-5 immunology
Interleukin-5 metabolism
Lymphocyte Depletion methods
Male
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Fluorescence
Neuralgia immunology
Neuralgia metabolism
Neuralgia physiopathology
Peripheral Nerve Injuries metabolism
Peripheral Nerve Injuries physiopathology
Sciatic Nerve immunology
Sciatic Nerve injuries
Sciatic Nerve physiopathology
Severity of Illness Index
T-Lymphocytes, Regulatory drug effects
T-Lymphocytes, Regulatory metabolism
Cytokines immunology
Hyperalgesia immunology
Peripheral Nerve Injuries immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 71
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 25461400
- Full Text :
- https://doi.org/10.1016/j.cyto.2014.10.028