RRC ID 35996
著者 Kobayashi Y, Kiguchi N, Fukazawa Y, Saika F, Maeda T, Kishioka S.
タイトル Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.
ジャーナル J Biol Chem
Abstract Peripheral neuroinflammation caused by activated immune cells can provoke neuropathic pain. Herein, we investigate the actions of macrophages and T cells through glucocorticoid-induced tumor neurosis factor receptor ligand (GITRL) and its receptor (GITR) in neuropathic pain. After partial sciatic nerve ligation (PSL) in enhanced green fluorescent protein (eGFP) chimeric mice generated by the transplantation of eGFP(+) bone marrow cells, eGFP(+) macrophages, and T cells markedly migrated to the injured site after PSL. Administration of agents to deplete macrophages (liposome-clodronate and Clophosome-A(TM)) or T cells (anti-CD4 antibody and FTY720) could suppress PSL-induced thermal hyperalgesia and tactile allodynia. The expression levels of co-stimulatory molecules GITRL and GITR were increased on infiltrating macrophages and T cells, respectively. The perineural injection of a GITRL neutralizing antibody that could inhibit the function of the GITRL-GITR pathway attenuated PSL-induced neuropathic pain. Additionally, the induction of inflammatory cytokines and the accumulation of GITR(+) T cells in the injured SCN were abrogated after macrophage depletion by Clophosome-A(TM). In conclusion, GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. The GITRL-GITR pathway might represent a novel target for the treatment of neuropathic pain.
巻・号 290(20)
ページ 12603-13
公開日 2015-5-15
DOI 10.1074/jbc.M115.636506
PII S0021-9258(20)33733-9
PMID 25787078
PMC PMC4432281
MeSH Animals Antibodies, Neutralizing / pharmacology Cell Communication* Cytokines / genetics Cytokines / metabolism Disease Models, Animal Glucocorticoid-Induced TNFR-Related Protein / genetics Glucocorticoid-Induced TNFR-Related Protein / metabolism* Lymphocyte Activation / drug effects Lymphocyte Activation / genetics Macrophages / metabolism* Macrophages / pathology Male Mice Mice, Transgenic Neuralgia / genetics Neuralgia / metabolism* Neuralgia / pathology Neuralgia / therapy T-Lymphocytes / metabolism* T-Lymphocytes / pathology Tumor Necrosis Factor Inhibitors Tumor Necrosis Factors / genetics Tumor Necrosis Factors / metabolism*
IF 4.238
引用数 33
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
実験動物マウス RBRC00267