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

Overview

Journal Autophagy

Specialty Cell Biology

Date 2016 May 13

PMID 27171064

Citations 164

Authors

Nunzia Pastore

Owen A Brady

Heba I Diab

Jose A Martina

Lu Sun

Tuong Huynh

Jeong-A Lim

Hossein Zare

Nina Raben

Andrea Ballabio

Rosa Puertollano

Affiliations

Soon will be listed here.

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.

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