Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs

The Journal of Cell Biology
Yun-Fen HungYi-Ping Hsueh

Abstract

Neuroinflammation is associated with diverse neurological disorders. Endosomal Toll-like receptors (TLRs) including TLR3, TLR7, and TLR8 cell-autonomously regulate neuronal differentiation. However, the mechanisms by which these three TLRs affect neuronal morphology are unclear. In this study, we compare these TLRs in mouse neurons. By combining in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling, we show that TLR8, TLR7, and TLR3 promote dendritic pruning via MYD88 signaling. However, they induce different transcriptomic profiles related to innate immunity, signaling, and neuronal development. The temporal expression patterns and the effects on neuronal morphology are not identical upon activation of these endosomal TLRs. Pathway analyses and in vitro studies specifically implicate mitogen-activated protein kinase signaling in TLR8-mediated dendritic pruning. We further show that TLR8 is more critical for dendritic arborization at a late development stage in vivo. The activation of TLR8, TLR7, or TLR3 results in dendritic shortening, and TLR7 and TLR3 but not TLR8 also control axonal growth. In-depth transcriptomic analyses show that TLRs use different downstream pathways to control neuronal morp...Continue Reading

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Citations

Feb 19, 2020·ELife·Guiyi LiAlicia Hidalgo
Dec 12, 2018·Frontiers in Molecular Neuroscience·Hsin-Yu LiuYi-Ping Hsueh
Jun 27, 2019·BioMed Research International·D M Abarca-MerlinL Alvarez-Arellano
Dec 18, 2019·Stem Cell Research & Therapy·Jhao-Yin LinHsing-I Huang
Nov 7, 2019·Journal of Biomedical Science·Chiung-Ya ChenYi-Ping Hsueh
Jul 30, 2020·Annual Review of Cell and Developmental Biology·Alice Lu-Culligan, Akiko Iwasaki
Jan 3, 2021·Cellular and Molecular Neurobiology·Fillipe M de AraújoMaria Trinidad Herrero
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Edward Beamer, Sonia A L Corrêa
Feb 14, 2021·International Immunopharmacology·Masoomeh MasoomikarimiReza Jafari
Oct 2, 2020·Brain, Behavior, and Immunity·Patricia SchroederSeija Lehnardt
Jul 30, 2020·Brain, Behavior, and Immunity·E K GranthamR A Harris
Apr 4, 2021·Viruses·Nicolás M S GálvezAlexis M Kalergis
May 8, 2020·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Francesca ArnaboldiIsabella Barajon

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Methods Mentioned

BETA
immunoprecipitation
coimmunoprecipitation
PCR
RNA-seq
Assay
transfection

Software Mentioned

Metascape
Prism
ImageQuant
Clampfit
Adobe
ImageQuant LAS 4000
Zen
VENNY
GraphPad
iT RNAi Designer

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