期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 12, 页码 6128-6135出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301603
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资金
- Ministerio de Educacion, Cultura y Deporte Formacion del Profesorado Universitario Proyecto [AP2010-5396]
- European Molecular Biology Organization Short Term Fellowship [ASTF 206-2012]
- Ministerio de Economia y Competividad [BFU2007-63712/BMC, BFU2011-23662]
- European Union's Seventh Framework Programme [241779]
- Singapore Immunology Network at A*STAR, Singapore
The three-prime repair exonuclease 1 (TREX1) is the most abundant exonuclease in mammalian cells. Mutations in Trex1 gene are being linked to the development of Aicardi-Goutie` res syndrome, an inflammatory disease of the brain, and systemic lupus erythematosus. In clinical cases and in a Trex1-deficient murine model, chronic production of type I IFN plays a pathogenic role. In this study, we demonstrate that Trex1(-/-) mice present inflammatory signatures in many different organs, including the brain. Trex1 is highly induced in macrophages in response to proinflammatory stimuli, including TLR7 and TLR9 ligands. Our findings show that, in the absence of Trex1, macrophages displayed an exacerbate proinflammatory response. More specifically, following proinflammatory stimulation, Trex1(-/-) macrophages exhibited an increased TNF-alpha and IFN-alpha production, higher levels of CD86, and increased Ag presentation to CD4(+) T cells, as well as an impaired apoptotic T cell clearance. These results evidence an unrevealed function of the Trex1 as a negative regulator of macrophage inflammatory activation and demonstrate that macrophages play a major role in diseases associated with Trex1 mutations, which contributes to the understanding of inflammatory signature in these diseases.
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