PMID- 34211474
OWN - NLM
STAT- MEDLINE
DCOM- 20211025
LR  - 20211025
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 12
DP  - 2021
TI  - Transcriptomic Analysis and C-Terminal Epitope Tagging Reveal Differential 
      Processing and Signaling of Endogenous TLR3 and TLR7.
PG  - 686060
LID - 10.3389/fimmu.2021.686060 [doi]
LID - 686060
AB  - Toll-like receptor (TLR) signaling is critical for defense against pathogenic 
      infection, as well as for modulating tissue development. Activation of different 
      TLRs triggers common inflammatory responses such as cytokine induction. Here, we 
      reveal differential impacts of TLR3 and TLR7 signaling on transcriptomic profiles 
      in bone marrow-derived macrophages (BMDMs). Apart from self-regulation, TLR3, but 
      not TLR7, induced expression of other TLRs, suggesting that TLR3 activation 
      globally enhances innate immunity. Moreover, we observed diverse influences of 
      TLR3 and TLR7 signaling on genes involved in methylation, caspase and autophagy 
      pathways. We compared endogenous TLR3 and TLR7 by using CRISPR/Cas9 technology to 
      knock in a dual Myc-HA tag at the 3' ends of mouse Tlr3 and Tlr7. Using anti-HA 
      antibodies to detect endogenous tagged TLR3 and TLR7, we found that both TLRs 
      display differential tissue expression and posttranslational modifications. 
      C-terminal tagging did not impair TLR3 activity. However, it disrupted the 
      interaction between TLR7 and myeloid differentiation primary response 88 (MYD88), 
      the Tir domain-containing adaptor of TLR7, which blocked its downstream signaling 
      necessary to trigger cytokine and chemokine expression. Our study demonstrates 
      different properties for TLR3 and TLR7, and also provides useful mouse models for 
      further investigation of these two RNA-sensing TLRs.
CI  - Copyright (c) 2021 Chen, Hung, Tsai, Shih, Chou, Lai, Wang and Hsueh.
FAU - Chen, Chiung-Ya
AU  - Chen CY
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Hung, Yun-Fen
AU  - Hung YF
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Tsai, Ching-Yen
AU  - Tsai CY
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Shih, Yi-Chun
AU  - Shih YC
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Chou, Ting-Fang
AU  - Chou TF
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Lai, Ming-Zong
AU  - Lai MZ
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Wang, Ting-Fang
AU  - Wang TF
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
FAU - Hsueh, Yi-Ping
AU  - Hsueh YP
AD  - Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210615
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Epitopes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TLR3 protein, mouse)
RN  - 0 (Tlr7 protein, mouse)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 7)
SB  - IM
MH  - Animals
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Epitopes/immunology/*metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Immunity, Innate
MH  - Macrophages/immunology/*metabolism
MH  - Male
MH  - Membrane Glycoproteins/genetics/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88/metabolism/physiology
MH  - Neurons/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 3/genetics/metabolism/*physiology
MH  - Toll-Like Receptor 7/genetics/metabolism/*physiology
PMC - PMC8240634
OTO - NOTNLM
OT  - MYD88
OT  - RNA-seq
OT  - epitope tagging
OT  - signalosome
OT  - toll-like receptor
OT  - transcriptomic analysis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/03 06:00
MHDA- 2021/10/26 06:00
PMCR- 2021/01/01
CRDT- 2021/07/02 06:37
PHST- 2021/03/26 00:00 [received]
PHST- 2021/06/01 00:00 [accepted]
PHST- 2021/07/02 06:37 [entrez]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/10/26 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2021.686060 [doi]
PST - epublish
SO  - Front Immunol. 2021 Jun 15;12:686060. doi: 10.3389/fimmu.2021.686060. eCollection 
      2021.