Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms

Abstract The innate immune system is the host’s initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead o...

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Main Authors: You-Sheng Lin, Yung-Chi Chang, Tzu-Yu Pu, Tsung-Hsien Chuang, Li-Chung Hsu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Biomedical Science
Subjects:
Online Access:https://doi.org/10.1186/s12929-025-01151-9
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author You-Sheng Lin
Yung-Chi Chang
Tzu-Yu Pu
Tsung-Hsien Chuang
Li-Chung Hsu
author_facet You-Sheng Lin
Yung-Chi Chang
Tzu-Yu Pu
Tsung-Hsien Chuang
Li-Chung Hsu
author_sort You-Sheng Lin
collection DOAJ
description Abstract The innate immune system is the host’s initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead or damaged cells, thereby initiating immune responses. Among PRRs, Toll-like receptors (TLRs) are well-studied and are located either on the cell surface or in endosomal compartments. Most endosomal TLRs specifically recognize nucleic acids and are thus referred to as nucleic acid (NA)-sensing TLRs. Upon activation, these receptors induce the production of inflammatory cytokines and type I interferons and initiate subsequent adaptive immunity. These immune responses work to suppress pathogens and inhibit tumor growth. However, excessive cytokine and interferon production can lead to various inflammatory diseases. This review focuses on mammalian nucleic acid-sensing TLRs, summarizing the molecular regulation of their activations, the impact of their dysregulation on human diseases, and therapeutic strategies that target these TLRs.
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institution OA Journals
issn 1423-0127
language English
publishDate 2025-06-01
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series Journal of Biomedical Science
spelling doaj-art-64c14c91ffbc494d93808db7e2e4e1b22025-08-20T02:07:41ZengBMCJournal of Biomedical Science1423-01272025-06-0132112810.1186/s12929-025-01151-9Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanismsYou-Sheng Lin0Yung-Chi Chang1Tzu-Yu Pu2Tsung-Hsien Chuang3Li-Chung Hsu4Institute of Molecular Medicine, National Taiwan UniversityInstitute of Molecular Medicine, National Taiwan UniversityInstitute of Molecular Medicine, National Taiwan UniversityCardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationInstitute of Molecular Medicine, National Taiwan UniversityAbstract The innate immune system is the host’s initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead or damaged cells, thereby initiating immune responses. Among PRRs, Toll-like receptors (TLRs) are well-studied and are located either on the cell surface or in endosomal compartments. Most endosomal TLRs specifically recognize nucleic acids and are thus referred to as nucleic acid (NA)-sensing TLRs. Upon activation, these receptors induce the production of inflammatory cytokines and type I interferons and initiate subsequent adaptive immunity. These immune responses work to suppress pathogens and inhibit tumor growth. However, excessive cytokine and interferon production can lead to various inflammatory diseases. This review focuses on mammalian nucleic acid-sensing TLRs, summarizing the molecular regulation of their activations, the impact of their dysregulation on human diseases, and therapeutic strategies that target these TLRs.https://doi.org/10.1186/s12929-025-01151-9Toll-like receptorsNucleic acid-sensingHuman disease
spellingShingle You-Sheng Lin
Yung-Chi Chang
Tzu-Yu Pu
Tsung-Hsien Chuang
Li-Chung Hsu
Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
Journal of Biomedical Science
Toll-like receptors
Nucleic acid-sensing
Human disease
title Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
title_full Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
title_fullStr Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
title_full_unstemmed Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
title_short Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms
title_sort involvement of nucleic acid sensing toll like receptors in human diseases and their controlling mechanisms
topic Toll-like receptors
Nucleic acid-sensing
Human disease
url https://doi.org/10.1186/s12929-025-01151-9
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