Toll-Like Receptor 7 (TLR7) Mediated Transcriptomic Changes on Human Mast Cells

Cho, Kyung‐Ah; Choi, Da Won; Park, Minhwa; Kim, Yu Hee; Woo, So Youn

doi:10.5021/ad.2021.33.5.402

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…For example, Castoldi et al demonstrated that lipopolysaccharide (LPS) triggered‐triacylglycerol synthesis is essential for inflammatory responses in macrophages (Castoldi et al, 2020). Cho et al reported that TLR7 activation is related with lipid droplet biogenesis in mast cells (Cho et al, 2021). While it is well‐accepted that TLRs are involved in modulating lipid homeostasis in immune cells (Jarc & Petan, 2020; Pereira‐Dutra et al, 2019), it is only recently shown that TLRs may also regulate lipid metabolism in other types of cells, such as liver cells.…”

Section: Introductionmentioning

confidence: 99%

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Intratracheal instillation of graphene oxide decreases anti‐virus responses and lipid contents via suppressing Toll‐like receptor 3 in mouse livers

Tang

Song

Zhao

et al. 2022

J of Applied Toxicology

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Recent studies revealed a causal relationship between Toll-like receptors (TLRs) and lipid droplet biogenesis. Interestingly, it has been reported before that nanomaterials (NMs) were capable to modulate TLRs, but it remains unclear if NMs could affect lipid levels via TLR signaling pathways. In this study, we investigated the influences of airway exposure to graphene oxide (GO) on TLR3 signaling pathways and lipid levels in mouse livers. Intratracheal instillation of GO (0.1, 1, and 5 mg/kg, once a day, totally 5 days) induced inflammatory cell infiltrations as indicated by hematoxylin-eosin (H&E) staining and fibrosis as indicated by Masson staining in lungs, accompanying with decreased TLR3 proteins. Consistently, a TLR3-regulated anti-virus protein, namely interferon induced protein with tetratricopeptide repeats 1 (IFIT1), as well as two TLR3-regulated lipid proteins, namely radical S-adenosyl methionine domain containing 2 (RSAD2) and perilipin 2 (PLIN2), were decreased in lungs. The protein levels of interferon-β in serum were also decreased. In livers, GO exposure induced disorganization of liver cells but not fibrosis. In agreement with the trends observed in lungs, TLR3, IFIT1, RSAD2, and PLIN2 proteins were decreased in livers. As a possible consequence, GO exposure dose-dependently decreased lipid levels in livers as indicated by oil red O and BODIPY 493/503 staining. We concluded that airway exposure to GO decreased anti-virus responses and lipid levels in mouse livers via the suppression of TLR3.

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Section: Introductionmentioning

confidence: 99%

“…For example, Castoldi et al demonstrated that lipopolysaccharide (LPS) triggered-triacylglycerol synthesis is essential for inflammatory responses in macrophages (Castoldi et al, 2020). Cho et al reported that TLR7 activation is related with lipid droplet biogenesis in mast cells (Cho et al, 2021).…”

mentioning

confidence: 99%

Intratracheal instillation of graphene oxide decreases anti‐virus responses and lipid contents via suppressing Toll‐like receptor 3 in mouse livers

Tang

Song

Zhao

et al. 2022

J of Applied Toxicology

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“…The total mapped read numbers were determined and normalized to detect the number of fragments per kilobase of transcript per million mapped reads and transcripts per kilobase. Differentially expressed gene analysis was performed using these values [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources

et al. 2023

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Background Blood transfusion is an essential part of medicine. However, many countries have been facing a national blood crisis. To address this ongoing blood shortage issue, there have been efforts to generate red blood cells (RBCs) in vitro, especially from human-induced pluripotent stem cells (hiPSCs). However, the best source of hiPSCs for this purpose is yet to be determined. Methods In this study, hiPSCs were established from three different hematopoietic stem cell sources—peripheral blood (PB), cord blood (CB) and bone marrow (BM) aspirates (n = 3 for each source)—using episomal reprogramming vectors and differentiated into functional RBCs. Various time-course studies including immunofluorescence assay, quantitative real-time PCR, flow cytometry, karyotyping, morphological analysis, oxygen binding capacity analysis, and RNA sequencing were performed to examine and compare the characteristics of hiPSCs and hiPSC-differentiated erythroid cells. Results hiPSC lines were established from each of the three sources and were found to be pluripotent and have comparable characteristics. All hiPSCs differentiated into erythroid cells, but there were discrepancies in differentiation and maturation efficiencies: CB-derived hiPSCs matured into erythroid cells the fastest while PB-derived hiPSCs required a longer time for maturation but showed the highest degree of reproducibility. BM-derived hiPSCs gave rise to diverse types of cells and exhibited poor differentiation efficiency. Nonetheless, erythroid cells differentiated from all hiPSC lines mainly expressed fetal and/or embryonic hemoglobin, indicating that primitive erythropoiesis occurred. Their oxygen equilibrium curves were all left-shifted. Conclusions Collectively, both PB- and CB-derived hiPSCs were favorably reliable sources for the clinical production of RBCs in vitro, despite several challenges that need to be overcome. However, owing to the limited availability and the large amount of CB required to produce hiPSCs, and the results of this study, the advantages of using PB-derived hiPSCs for RBC production in vitro may outweigh those of using CB-derived hiPSCs. We believe that our findings will facilitate the selection of optimal hiPSC lines for RBC production in vitro in the near future.

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TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase

Liu,

Haw,

Starkey

et al. 2023

Nat Commun

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Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

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Toll-Like Receptor 7 (TLR7) Mediated Transcriptomic Changes on Human Mast Cells

Cited by 4 publications

References 20 publications

Intratracheal instillation of graphene oxide decreases anti‐virus responses and lipid contents via suppressing Toll‐like receptor 3 in mouse livers

Intratracheal instillation of graphene oxide decreases anti‐virus responses and lipid contents via suppressing Toll‐like receptor 3 in mouse livers

In vitro erythrocyte production using human-induced pluripotent stem cells: determining the best hematopoietic stem cell sources

TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase

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