Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections

Abstract Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain...

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Main Authors: Ruiqi Li, Fan Gu, Linlin Peng, Tingting Huan, Zhuo Zhou, Yaling Song, Jinmei He, Kaili Ye, Yao Sun, Tiejun Li, Miao He, Zhuan Bian, Wei Yin
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202406684
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author Ruiqi Li
Fan Gu
Linlin Peng
Tingting Huan
Zhuo Zhou
Yaling Song
Jinmei He
Kaili Ye
Yao Sun
Tiejun Li
Miao He
Zhuan Bian
Wei Yin
author_facet Ruiqi Li
Fan Gu
Linlin Peng
Tingting Huan
Zhuo Zhou
Yaling Song
Jinmei He
Kaili Ye
Yao Sun
Tiejun Li
Miao He
Zhuan Bian
Wei Yin
author_sort Ruiqi Li
collection DOAJ
description Abstract Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental pulp is an ideal model for comprehensively studying the TLS. In the present study, single‐cell RNA sequencing of healthy and inflamed human dental pulp reveals known markers of TLS, including C‐C motif chemokine ligand 19 (CCL19), lysosome‐associated membrane glycoprotein 3 (LAMP3), CC chemokine receptor 7 (CCR7), and CD86, present in inflamed dental pulp. Compared with the healthy pulp, types and proportions of immune cells increase, along with enhanced cellular communication. Multiple immunofluorescence staining reveals that typical TLS emerges in dental pulp with pulpitis, consistent with the high expression of CC chemokine ligand 3 (CCL3), which may be a key driver of TLS formation. Moreover, TLS is also observed in a mouse model of pulpitis. These findings collectively offer insights into the formation and function of TLS in response to infection.
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spelling doaj-art-8d5f77b2d4a848f298367a9f1f2401a12025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202406684Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial InfectionsRuiqi Li0Fan Gu1Linlin Peng2Tingting Huan3Zhuo Zhou4Yaling Song5Jinmei He6Kaili Ye7Yao Sun8Tiejun Li9Miao He10Zhuan Bian11Wei Yin12State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaDepartment of Cariology and Endodontics (II) Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaDepartment of Implantology Shanghai Engineering Research Center of Tooth Restoration and Regeneration Stomatological Hospital and Dental School of Tongji University Shanghai 200092 ChinaDepartment of Oral Pathology National Center of Stomatology National Clinical Research Center for Oral Diseases National Engineering Laboratory for Digital and Material Technology of Stomatology Beijing Key Laboratory of Digital Stomatology Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health NMPA Key Laboratory for Dental Materials Peking University School and Hospital of Stomatology Beijing 100081 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan 430079 ChinaAbstract Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental pulp is an ideal model for comprehensively studying the TLS. In the present study, single‐cell RNA sequencing of healthy and inflamed human dental pulp reveals known markers of TLS, including C‐C motif chemokine ligand 19 (CCL19), lysosome‐associated membrane glycoprotein 3 (LAMP3), CC chemokine receptor 7 (CCR7), and CD86, present in inflamed dental pulp. Compared with the healthy pulp, types and proportions of immune cells increase, along with enhanced cellular communication. Multiple immunofluorescence staining reveals that typical TLS emerges in dental pulp with pulpitis, consistent with the high expression of CC chemokine ligand 3 (CCL3), which may be a key driver of TLS formation. Moreover, TLS is also observed in a mouse model of pulpitis. These findings collectively offer insights into the formation and function of TLS in response to infection.https://doi.org/10.1002/advs.202406684carieschemokinesdental pulpimmune cellspulpitistertiary lymphoid structure (TLS)
spellingShingle Ruiqi Li
Fan Gu
Linlin Peng
Tingting Huan
Zhuo Zhou
Yaling Song
Jinmei He
Kaili Ye
Yao Sun
Tiejun Li
Miao He
Zhuan Bian
Wei Yin
Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
Advanced Science
caries
chemokines
dental pulp
immune cells
pulpitis
tertiary lymphoid structure (TLS)
title Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
title_full Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
title_fullStr Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
title_full_unstemmed Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
title_short Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections
title_sort tertiary lymphoid structure in dental pulp the role in combating bacterial infections
topic caries
chemokines
dental pulp
immune cells
pulpitis
tertiary lymphoid structure (TLS)
url https://doi.org/10.1002/advs.202406684
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