Macrophage-T Cell Interactions Mediate Neuropathic Pain through the Glucocorticoid-induced Tumor Necrosis Factor Ligand System

• DOI: 10.1074/jbc.m115.636506
• Publication Date: 2015-03-19T02:42:47Z
• Authors: Yuka Kobayashi; Norikazu Kiguchi; Yohji Fukazawa; Fumihiro Saika; Takehiko Maeda; Shiroh Kishioka
• Keywords: Male; 0301 basic medicine; Macrophages; T-Lymphocytes; Mice, Transgenic; Cell Communication; Lymphocyte Activation; Antibodies, Neutralizing; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Glucocorticoid-Induced TNFR-Related Protein; Tumor Necrosis Factors; Animals; Cytokines; Neuralgia; Tumor Necrosis Factor Inhibitors

Peripheral neuroinflammation caused by activated immune cells can provoke neuropathic pain. Herein, we investigate the actions of macrophages and T through glucocorticoid-induced tumor neurosis factor receptor ligand (GITRL) its (GITR) in After partial sciatic nerve ligation (PSL) enhanced green fluorescent protein (eGFP) chimeric mice generated transplantation eGFP(+) bone marrow cells, macrophages, markedly migrated to injured site after PSL. Administration agents deplete (liposome-clodronate Clophosome-A(TM)) or (anti-CD4 antibody FTY720) could suppress PSL-induced thermal hyperalgesia tactile allodynia. The expression levels co-stimulatory molecules GITRL GITR were increased on infiltrating respectively. perineural injection a neutralizing that inhibit function GITRL-GITR pathway attenuated Additionally, induction inflammatory cytokines accumulation GITR(+) SCN abrogated macrophage depletion Clophosome-A(TM). In conclusion, expressed drives cytokine release cell activation, resulting pain via GITR-dependent actions. might represent novel target for treatment