T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression.
Interleukin (IL)-17A, a recently described novel T cell cytokine, orchestrates inflammation in a variety of immune-mediated diseases. In the present investigation, we analyzed the temporal gene expression pattern of IL-17A and its main regulators IL-23 and IL-15 after chronic constriction injury (CCI) of the sciatic nerve, a lesion paradigm inducing neuropathic pain, by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in mice. IL-17A displayed a monophasic expression in degenerating nerves at day 7 after CCI while transcripts for the IL-17A regulatory cytokines IL-23 and IL-15 peaked earlier. Accordingly, IL-17A positive T cells were detectable within the endoneurium of the injured nerves by immunocytochemistry. In support of a crucial role of T cell inflammation, RAG-1 knockout mice lacking functional T lymphocytes did not express IL-17A mRNA in distal nerve segments following CCI. Interestingly, T cell deficiency was associated with less thermal hyperalgesia and reduced mRNA levels for the macrophage marker molecule F4/80 and the chemokine macrophage chemoattractant protein-1 (MCP-1) after CCI. Our study supports the notion that T cells and T-cell-derived cytokines contribute to the inflammatory response after peripheral nerve injury.
Kleinschnitz
Christoph
C
Department of Neurology, Julius-Maximilians-Universität, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany.
Hofstetter
Harald H
HH
Meuth
Sven G
SG
Braeuninger
Stefan
S
Sommer
Claudia
C
Stoll
Guido
G