Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8258782 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2018 | 19 Pages |
Abstract
Together with ROS, the second messenger ion Ca2 + plays a central role in immune regulation. TRPM2 (Transient Receptor Potential Melastatin 2) is a Ca2 +-permeable ion channel that is activated under conditions of oxidative stress. The Trpm2 gene is located on human Chromosome 21 (Hsa21). TRPM2 is strongly represented in innate immune cells, and numerous studies have documented its role in modulating inflammation. We have previously found that as a result of suboptimal cytokine production, TRPM2â/â mice are highly susceptible to the bacterial pathogen Listeria monocytogenes (Lm). We therefore used Lm infection to trigger and characterize immune responsiveness in the DS mouse model Dp10(yey), and to investigate the potential contribution of TRPM2. In comparison to wildtype (WT), Dp10(yey) mice show an increased resistance against Lm infection and higher IFNγ serum concentrations. Using a gene elimination approach, we show that these effects correlate with Trpm2 gene copy number, supporting the notion that Trpm2 might promote hyperinflammation in DS.
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Authors
Fabienne Gally, Deviyani M. Rao, Carsten Schmitz, Kelley L. Colvin, Michael E. Yeager, Anne-Laure Perraud,