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.

TFEB and TFE3 Cooperate in the Regulation of the Innate Immune Response in Activated Macrophages / Pastore, Nunzia; Brady, Owen A; Diab, Heba I; Martina, José A; Sun, Lu; Huynh, Tuong; Lim, Jeong A; Zare, Hossein; Raben, Nina; Ballabio, Andrea; Puertollano, Rosa. - In: AUTOPHAGY. - ISSN 1554-8627. - (2016), pp. 0-00. [10.1080/15548627.2016.1179405]

TFEB and TFE3 Cooperate in the Regulation of the Innate Immune Response in Activated Macrophages

Pastore, Nunzia;BALLABIO, ANDREA;
2016

Abstract

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.
2016
TFEB and TFE3 Cooperate in the Regulation of the Innate Immune Response in Activated Macrophages / Pastore, Nunzia; Brady, Owen A; Diab, Heba I; Martina, José A; Sun, Lu; Huynh, Tuong; Lim, Jeong A; Zare, Hossein; Raben, Nina; Ballabio, Andrea; Puertollano, Rosa. - In: AUTOPHAGY. - ISSN 1554-8627. - (2016), pp. 0-00. [10.1080/15548627.2016.1179405]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/634135
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