Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmune Diseases / immunology
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Autoimmune Diseases / mortality
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Autoimmune Diseases of the Nervous System* / immunology
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Autoimmune Diseases of the Nervous System* / metabolism
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Calcium / metabolism
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Cell Proliferation
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Cells, Cultured
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Cytokines / metabolism
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Disease Models, Animal
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Encephalomyelitis, Autoimmune, Experimental* / immunology
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Encephalomyelitis, Autoimmune, Experimental* / metabolism
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Humans
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Inflammation / metabolism
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Mice
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Neurons / metabolism
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Neurons / physiology
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Oxidative Stress
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Spleen / cytology
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T-Lymphocytes* / immunology
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T-Lymphocytes* / metabolism
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T-Lymphocytes* / pathology
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TRPM Cation Channels* / deficiency
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TRPM Cation Channels* / genetics
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TRPM Cation Channels* / metabolism
Substances
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Cytokines
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TRPM Cation Channels
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TRPM2 protein, mouse
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Calcium
Grants and funding
This study was supported by an intramural grant of the University of Münster (IMF – ME121010) to NM. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.