Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses

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Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses

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Title: Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses
Author: Bai, A; Kokkotou, E; Zheng, Y; Robson, S C

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Citation: Bai, A, E Kokkotou, Y Zheng, and S C Robson. 2015. “Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses.” Cell Death & Disease 6 (7): e1828. doi:10.1038/cddis.2015.178. http://dx.doi.org/10.1038/cddis.2015.178.
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Abstract: Acid sphingomyelinase (ASM), a lipid hydrolase enzyme, has the potential to modulate various cellular activation responses via the generation of ceramide and by interaction with cellular receptors. We have hypothesized that ASM modulates CD4+ T-cell receptor activation and impacts immune responses. We first observed interactions of ASM with the intracellular domains of both CD3 and CD28. ASM further mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation and alters CD4+ T-cell activation signals by generating ceramide. We noted that various pharmacological inhibitors of ASM or knockdown of ASM using small hairpin RNA inhibit CD3/CD28-mediated CD4+ T-cell proliferation and activation. Furthermore, such blockade of ASM bioactivity by biochemical inhibitors and/or molecular-targeted knockdown of ASM broadly abrogate T-helper cell responses. In conclusion, we detail immune, pivotal roles of ASM in adaptive immune T-cell responses, and propose that these pathways might provide novel targets for the therapy of autoimmune and inflammatory diseases.
Published Version: doi:10.1038/cddis.2015.178
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650726/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993605
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