Pattern recognition receptors: function, regulation and therapeutic potential

Abstract Pattern recognition receptors (PRRs) are sensors in the immune system, detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They serve as essential links between the innate and adaptive immune responses, initiating defense mechanisms aga...

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Main Authors: Ruochan Chen, Ju Zou, Jiawang Chen, Xiao Zhong, Rui Kang, Daolin Tang
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-025-02264-1
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author Ruochan Chen
Ju Zou
Jiawang Chen
Xiao Zhong
Rui Kang
Daolin Tang
author_facet Ruochan Chen
Ju Zou
Jiawang Chen
Xiao Zhong
Rui Kang
Daolin Tang
author_sort Ruochan Chen
collection DOAJ
description Abstract Pattern recognition receptors (PRRs) are sensors in the immune system, detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They serve as essential links between the innate and adaptive immune responses, initiating defense mechanisms against pathogens and maintaining immune homeostasis. This review examines the classification, structure, and signaling cascades of key PRR families, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), AIM2-like receptors (ALRs), and others. It explores the dual roles of PRRs in immune defense and regulation, particularly through inhibitory PRRs (iPRRs), which prevent immune overactivation. The review also investigates the ligand recognition mechanisms and signaling pathways, highlighting the involvement of PRRs in disease progression and immune modulation. Notable signaling pathways, including NF-κB, MAPK, cGAS-STING, and MYD88-mediated and non-MYD88-mediated cascades, are discussed in the context of immune responses. Mechanisms that fine-tune PRR-mediated responses include transcriptional and fpost-transcriptional regulation, protein degradation, subcellular localization, and the recruitment of amplifiers and inhibitors, along with metabolic and microbial factors. These regulatory strategies ensure immune signaling remains adaptable and precise, preventing excessive inflammation. The review also explores the therapeutic potential of targeting PRRs in treating infectious, inflammatory, autoimmune, and malignant diseases, underscoring their importance in advancing immunological research and precision medicine.
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spelling doaj-art-846f70fce3d045b493d71f1dd5ca893d2025-08-20T04:02:45ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-07-0110115310.1038/s41392-025-02264-1Pattern recognition receptors: function, regulation and therapeutic potentialRuochan Chen0Ju Zou1Jiawang Chen2Xiao Zhong3Rui Kang4Daolin Tang5Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South UniversityHunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South UniversityHunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South UniversityHunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South UniversityDepartment of Surgery, UT Southwestern Medical CenterDepartment of Surgery, UT Southwestern Medical CenterAbstract Pattern recognition receptors (PRRs) are sensors in the immune system, detecting pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They serve as essential links between the innate and adaptive immune responses, initiating defense mechanisms against pathogens and maintaining immune homeostasis. This review examines the classification, structure, and signaling cascades of key PRR families, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), AIM2-like receptors (ALRs), and others. It explores the dual roles of PRRs in immune defense and regulation, particularly through inhibitory PRRs (iPRRs), which prevent immune overactivation. The review also investigates the ligand recognition mechanisms and signaling pathways, highlighting the involvement of PRRs in disease progression and immune modulation. Notable signaling pathways, including NF-κB, MAPK, cGAS-STING, and MYD88-mediated and non-MYD88-mediated cascades, are discussed in the context of immune responses. Mechanisms that fine-tune PRR-mediated responses include transcriptional and fpost-transcriptional regulation, protein degradation, subcellular localization, and the recruitment of amplifiers and inhibitors, along with metabolic and microbial factors. These regulatory strategies ensure immune signaling remains adaptable and precise, preventing excessive inflammation. The review also explores the therapeutic potential of targeting PRRs in treating infectious, inflammatory, autoimmune, and malignant diseases, underscoring their importance in advancing immunological research and precision medicine.https://doi.org/10.1038/s41392-025-02264-1
spellingShingle Ruochan Chen
Ju Zou
Jiawang Chen
Xiao Zhong
Rui Kang
Daolin Tang
Pattern recognition receptors: function, regulation and therapeutic potential
Signal Transduction and Targeted Therapy
title Pattern recognition receptors: function, regulation and therapeutic potential
title_full Pattern recognition receptors: function, regulation and therapeutic potential
title_fullStr Pattern recognition receptors: function, regulation and therapeutic potential
title_full_unstemmed Pattern recognition receptors: function, regulation and therapeutic potential
title_short Pattern recognition receptors: function, regulation and therapeutic potential
title_sort pattern recognition receptors function regulation and therapeutic potential
url https://doi.org/10.1038/s41392-025-02264-1
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AT jiawangchen patternrecognitionreceptorsfunctionregulationandtherapeuticpotential
AT xiaozhong patternrecognitionreceptorsfunctionregulationandtherapeuticpotential
AT ruikang patternrecognitionreceptorsfunctionregulationandtherapeuticpotential
AT daolintang patternrecognitionreceptorsfunctionregulationandtherapeuticpotential