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Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis
To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were d...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812403/ https://www.ncbi.nlm.nih.gov/pubmed/35126357 http://dx.doi.org/10.3389/fimmu.2021.792901 |
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author | Tian, Yixiao Huang, Biqing Li, Jing Tian, Xinping Zeng, Xiaofeng |
author_facet | Tian, Yixiao Huang, Biqing Li, Jing Tian, Xinping Zeng, Xiaofeng |
author_sort | Tian, Yixiao |
collection | PubMed |
description | To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK. |
format | Online Article Text |
id | pubmed-8812403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88124032022-02-04 Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis Tian, Yixiao Huang, Biqing Li, Jing Tian, Xinping Zeng, Xiaofeng Front Immunol Immunology To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK. Frontiers Media S.A. 2022-01-20 /pmc/articles/PMC8812403/ /pubmed/35126357 http://dx.doi.org/10.3389/fimmu.2021.792901 Text en Copyright © 2022 Tian, Huang, Li, Tian and Zeng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Tian, Yixiao Huang, Biqing Li, Jing Tian, Xinping Zeng, Xiaofeng Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title | Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title_full | Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title_fullStr | Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title_full_unstemmed | Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title_short | Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis |
title_sort | identification of the association between toll-like receptors and t-cell activation in takayasu’s arteritis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812403/ https://www.ncbi.nlm.nih.gov/pubmed/35126357 http://dx.doi.org/10.3389/fimmu.2021.792901 |
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