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Bimolecular Fluorescence Complementation
Published on: April 15, 2011
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IRF8 and BATF3 interaction enhances the cDC1 specific Pfkfb3 gene expression.
Kuldeep Singh Chauhan1, Annesa Das2, Hemant Jaiswal3
1Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, India; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA(1).
Cellular Immunology
|December 30, 2021
Summary
This study reveals how transcription factors IRF8 and BATF3 regulate the development of classical dendritic cell type 1 (cDC1). It identifies Pfkfb3 as a key metabolic gene directly controlled by these factors, impacting cDC1 numbers.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Dendritic cells (DCs) orchestrate innate and adaptive immunity through diverse subtypes.
- DC development relies on intricate transcription factor interactions.
- Previous work showed Batf3 and Id2 synergize with Irf8 for cDC1 development.
Purpose of the Study:
- To elucidate the molecular mechanisms governing cDC1 development.
- To identify specific genes and interactions regulating cDC1 differentiation.
- To understand the role of metabolic pathways in cDC1 biology.
Main Methods:
- Bi-molecular fluorescence complementation assay to study protein interactions.
- Genome-wide recruitment analysis of transcription factors IRF8 and BATF3.
- Analysis of gene expression in knockout and conditional knockout mouse models (Irf8-/-, Irf8R294C, Batf3DCKO).
- In vitro FLDC cultures and in vivo mouse spleen studies with PFK15 inhibitor.
Main Results:
- IRF8 directly interacts with BATF3; ID2 may act independently in cDC1 development.
- Overlapping binding sites of IRF8 and BATF3 identified, pinpointing the Pfkfb3 gene promoter.
- Splenic cDC1 subtypes show enhanced Pfkfb3 expression, directly regulated by Irf8 and Batf3.
- Inhibition of PFKFB3 activity reduces cDC1 populations in vitro and in vivo.
Conclusions:
- Identified a direct regulatory link between IRF8, BATF3, and the metabolic gene Pfkfb3 in cDC1 development.
- Pfkfb3 plays a crucial role in cDC1 biology and proliferation.
- This study sheds light on the metabolic regulation of dendritic cell subtypes.
