期刊
AUTOPHAGY
卷 12, 期 8, 页码 1240-1258出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1179405
关键词
autophagy; immune response; macrophages; Tfe3; Tfeb
类别
资金
- Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI)
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) of the NIH
- CRADA
- US National Institutes of Health [R01-NS078072]
- Beyond Batten Disease Foundation
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006151] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIAAR041099] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS078072] Funding Source: NIH RePORTER
The activation of transcription factors is critical to ensure an effective defense against pathogens. In this study we identify a critical and complementary role of the transcription factors TFEB and TFE3 in innate immune response. By using a combination of chromatin immunoprecipitation, CRISPR-Cas9-mediated genome-editing technology, and in vivo models, we determined that TFEB and TFE3 collaborate with each other in activated macrophages and microglia to promote efficient autophagy induction, increased lysosomal biogenesis, and transcriptional upregulation of numerous proinflammatory cytokines. Furthermore, secretion of key mediators of the inflammatory response (CSF2, IL1B, IL2, and IL27), macrophage differentiation (CSF1), and macrophage infiltration and migration to sites of inflammation (CCL2) was significantly reduced in TFEB and TFE3 deficient cells. These new insights provide us with a deeper understanding of the transcriptional regulation of the innate immune response.
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