TRPM2 cation channels modulate T cell effector functions and contribute to autoimmune CNS inflammation.
TRPM2, a highly Ca(2+)-permeable member of the transient receptor potential melastatin-related (TRPM) family of cation channels, is expressed in cells of the immune system. We demonstrate firstly that TRPM2 cation channels on T cells critically influence T cell proliferation and proinflammatory cytokine secretion following polyclonal T cell receptor stimulation. Consistently, trpm2-deficient mice exhibited an attenuated clincal phenotype of experimental autoimmune encephalomyelitis (EAE) with reduced inflammatory and demyelinating spinal cord lesions. Importantly, trmp2-deficient T cells were as susceptible as wildtype T cells to oxidative stress-induced cell death as it occurs in inflammatory CNS lesions. This supports the notion that the attenuated EAE phenotype is mainly due to reduced T cell effector functions but unaffected by potential modulation of T cell survival at the site of inflammation. Our findings suggest TRPM2 cation channels as a potential target for treating autoimmune CNS inflammation.
Department of Neurology-Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Münster, Germany. nico.melzer@ukmuenster.de
Nico
N
Melzer
Gordon
G
Hicking
Kerstin
K
Göbel
Heinz
H
Wiendl
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000401:mortality; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050053:TRPM Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; D002118:Calcium