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- W4313385629 abstract "Abstract Th17 cells are implicated in autoimmune disease, including attack of the central nervous system (CNS) in multiple sclerosis. β-site APP-cleaving enzyme 1 (BACE1) is a membrane protease expressed in neurons and astrocytes. BACE1 is most well known for its role in promoting neurodegeneration in Alzheimer’s disease by cleaving amyloid precursor protein, although it also plays a role in central nervous system myelination. BACE1 has also been reported to contribute to lesion severity following brain injury, as has IL-17, although these two molecules have not previously been linked. We observed that BACE1 is upregulated in experimental autoimmune encephalomyelitis (EAE) lesions, a mouse model of multiple sclerosis, suggesting a role in autoimmune CNS damage. Surprisingly, we discovered that Bace1-deficient MOG-reactive T cells were defective in IL-17A production. In vitro differentiated Th17 cells were similarly defective in IL-17A. Conversely, overexpression of Bace1 increased IL-17A production. Transfer experiments demonstrated that BACE1 deficiency in T cells impairs their pathogenic function and confers resistance in EAE. Although the impact on IL-17A production was dramatic, there was only a mild defect in expression of RORγt, IL-23R and other prototypic Th17-associated molecules such as IL-17F. This was confirmed by RNA-Seq, which revealed other potential Bace1 targets outside the classic Th17 armory. Therefore, we propose that Bace1 is a novel modulator of the effector function of Th17 cells, particularly IL-17A production." @default.
- W4313385629 created "2023-01-06" @default.
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- W4313385629 date "2016-05-01" @default.
- W4313385629 modified "2023-10-16" @default.
- W4313385629 title "BACE1: a novel player in the pathogenesis of Th17 cells in EAE" @default.
- W4313385629 doi "https://doi.org/10.4049/jimmunol.196.supp.189.11" @default.
- W4313385629 hasPublicationYear "2016" @default.
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