The mucosal immune system in the oral cavity—an orchestra of T cell diversity
Open accessAbstract
The mucosal immune system defends against a vast array of pathogens, yet it exhibits limited responses to commensal microorganisms under healthy conditions. The oral-pharyngeal cavity, the gateway for both the gastrointestinal and respiratory tracts, is composed of complex anatomical structures and is constantly challenged by antigens from air and food. The mucosal immune system of the oral-pharyngeal cavity must prevent pathogen entry while maintaining immune homeostasis, which is achieved via a range of mechanisms that are similar or different to those utilized by the gastrointestinal immune system. In this review, we summarize the features of the mucosal immune system, focusing on T cell subsets and their functions. We also discuss our current understanding of the oral-pharyngeal mucosal immune system. The diverse immune responses provided by T cells in the lining of the oral cavity have been reviewed by US and Chinese researchers. The oral-pharyngeal cavity is the gateway to the gastrointestinal (GI) and respiratory tracts, and is exposed to microbes, food particles and other substances. The oral mucosal layers contain many different types of T cells that protect against infection but detailed knowledge of their function is limited. WanJun Chen, Qian-Ming Chen and co-workers at the National Institutes of Health in Maryland, and Sichuan University in Chengdu, base their review on the more established knowledge of the GI mucosal system. They find that the oral cavity lining has many similar functions to the lining of the GI but produces some unique signalling proteins. The authors highlight the need for more research into this important immune barrier.
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Specialized immune-cell networks in the oral cavity respond to the challenges of this fluctuating environment via tissue-specific cues and exclusive immunologic responses that are tailored to the oral cavity.
“Regardless, specialized immune‐cell networks in the oral cavity respond to the challenges of this fluctuating environment via tissue‐specific cues and exclusive immunologic responses that are tailored to the oral cavity.53, 106, 107, 108”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [107]
While the inflammation characteristics of gingivitis are mostly reversible, periodontitis results in long-term, irreversible damage to the periodontal tissues and alveolar bone that manifests as tissue detachment from the tooth, formation of a pocket wherein pathogenic bacteria can proliferate further, and eventual tooth loss in advanced stages of the disease.
“While the inflammation characteristics of gingivitis are mostly reversible, periodontitis results in long‐term, irreversible damage to the periodontal tissues and alveolar bone that manifests as tissue detachment from the tooth, formation of a pocket wherein pathogenic bacteria can proliferate further, and eventual tooth loss in advanced stages of the disease.192, 193, 194, 195”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [194]
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Anderson, M. K. (2013) · Nature Immunology · doi:10.1038/ni.2544 · Cited by 7 · see citing works
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The oral microbiome: Role of key organisms and complex networks in oral health and disease
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L. (2021) · Periodontology 2000 · doi:10.1111/prd.12393 · Cited by 755 · see citing works
An Overview of Physical, Microbiological and Immune Barriers of Oral Mucosa
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“The mucosal immune system of the oral cavity is constantly exposed to tissue-specific signals, including a rich community of commensal microbes and their metabolites, continuous tissue damage from mastication, antigens from food and airborne particles, which present potential challenges to the homeostasis of the oral…”
BackgroundOral microbiome: possible harbinger for children’s health
Xiao, J., Fiscella, K. A., & Gill, S. R. (2020) · International Journal of Oral Science · doi:10.1038/s41368-020-0082-x · Cited by 223 · see citing works
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Self-citationHIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation
Heron, S., & Elahi, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00241 · Cited by 104 · see citing works
“Since the gut-associated lymphoid tissue (GALT) is so similar in structure and in resident immune cells to the mucosal-associated lymphoid tissue of the oral cavity (16), it could be hypothesized that HIV infection may result in the induction of similar patterns of destruction in the oral mucosal tissues.”
BackgroundDorta-Estremera, S. M., Hegde, V. L., Slay, R., Sun, R., Yanamandra, A. V., Nicholas, C., Nookala, S. M. K., Sierra, G., Curran, M. A., & Sastry, K. J. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0728-4 · Cited by 104 · see citing works
Targeting Proteases for Treating COVID-19
Luan, B., Huynh, T., Cheng, X. M., Lan, G., & Wang, H. (2020) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c00430 · Cited by 108 · see citing works
Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease
Ahn‐Jarvis, J. H., Parihar, A., & Doseff, A. I. (2019) · Antioxidants · doi:10.3390/antiox8070202 · Cited by 95 · see citing works
“Hence, providing beneficial effects on specialized MALT structures of the oral cavity, antigen presenting cells of the oral epithelium, and salivary antibodies in a similar manner to flavonoids on gut immunity [157,158], as shown in Figure 2A.”
BackgroundRecent advances in graphene-based nanobiosensors for salivary biomarker detection
Goldoni, R., Farronato, M., Connelly, S., Tartaglia, G. M., & Yeo, W. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112723 · Cited by 96 · see citing works
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The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw
Zhang, W., Gao, L., Ren, W., Li, S., Zheng, J., Li, S., Jiang, C., Yang, S., & Zhi, K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.606043 · Cited by 76 · see citing works
“The mucosal immune system defenses against a variety of microbes and maintains the immune homeostasis in the oral cavity under healthy conditions (15).”
BackgroundNicu, E. A., Rijkschroeff, P., Wartewig, E., Nazmi, K., & Loos, B. G. (2018) · BMC Oral Health · doi:10.1186/s12903-018-0615-2 · Cited by 76 · see citing works
das Neves, J., Arzi, R. S., & Sosnik, A. (2020) · Chemical Society Reviews · doi:10.1039/c8cs00948a · Cited by 72 · see citing works
Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis
Suárez, L. J., Arboleda, S., Angelov, N., & Arce, R. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.705206 · Cited by 71 · see citing works
Modified chitosan: Insight on biomedical and industrial applications
Edo, G. I., Yousif, E. A., & Al-Mashhadani, M. H. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.133526 · Cited by 69 · see citing works
Coffey, J. W., Gaiha, G. D., & Traverso, G. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-030320-092348 · Cited by 67 · see citing works
“The major effector sites of the GI tract are the LP (24); the surface of the epithelium (24); and, in the oral cavity, the secretory saliva glands (58, 59).”
BackgroundMultifunctional polysaccharide composited microneedle for oral ulcers healing
Zeng, Y., Gao, Y., He, L., Ge, W., Liu, J., Yu, Y., & Xie, X. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100782 · Cited by 66 · see citing works
“Disorders of the immune system also play a crucial role in the development of oral ulcers [10].”
BackgroundKozak, M., & Hu, J. (2023) · Vaccines · doi:10.3390/vaccines11030695 · Cited by 70 · see citing works
“Vaccine Delivery Routes (insets (L,R): [71,72]).”
Davis, A. S. W., Roozen, H. N., Dufort, M. J., DeBerg, H. A., Delaney, M. A., Mair, F., Erickson, J. R., Slichter, C. K., Berkson, J. D., Klock, A. M., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw8718 · Cited by 61 · see citing works
“Inflammation involves changes in vasculature, secretion of inflammatory mediators, and cellular infiltrate (28) that together alter tissue architecture and the local immune network (29).”
BackgroundPark, J., Chung, H., DiPalma, D. T., Tai, X., & Park, J. (2018) · Mucosal Immunology · doi:10.1038/s41385-018-0027-2 · Cited by 52 · see citing works
“On the other hand, it also needs to remain immunocompetent against invading microbial pathogens.(1) In lymphoid tissues, the balance of tolerance vs.”
BackgroundRelationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis
Pólvora, T. L. S., Nobre, Á. V. V., Tirapelli, C., Taba, M., de Macedo, L. D., Santana, R. D. C., Pozzetto, B., Lourenço, A. G., & Motta, A. C. F. (2018) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2018.1459571 · Cited by 51 · see citing works
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Immunomodulatory role of oral microbiota in inflammatory diseases and allergic conditions
Moreno, C. M., Boeree, E., Freitas, C. M. T., & Weber, K. S. (2023) · Frontiers in Allergy · doi:10.3389/falgy.2023.1067483 · Cited by 51 · see citing works
“However, epithelia in the mouth are multilayered, vary in their permeability and function, and include keratinized and non-keratinized epithelia which differs from the characteristics of intestinal epithelia (8, 13).”
BackgroundInfluentialInflammatory and Immunological Basis of Periodontal Diseases
Baima, G., Arce, M., Romandini, M., & Dyke, T. E. V. (2025) · Journal of Periodontal Research · doi:10.1111/jre.70040 · Cited by 49 · see citing works
Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions
Li, S., Su, B., He, Q., Wu, H., & Zhang, T. (2021) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001825 · Cited by 46 · see citing works
“The structure and network of the oral mucosal immune systemhave also beendescribed tobe similar to those of the gastrointestinal mucosal immune system.([25]) This accumulating evidence suggests that oral microbiota may be similar to gut microbiota, both of which might induce systemic diseases through systemic transloc…”
BackgroundImpact of the food grade heat-killed probiotic and postbiotic oral lozenges in oral hygiene
Lin, C., Chen, Y., Ho, H.-H., Kuo, Y., Lin, W., Chen, J., Lin, J., Liu, C., Lin, C.-H., Yeh, Y., et al. (2022) · Aging · doi:10.18632/aging.203923 · Cited by 43 · see citing works
“The mucosal immune system of the oropharyngeal cavity, which is the opening gate for digestive and respiratory systems, plays a crucial role in preventing pathogen entry into the human body [1].”
BackgroundWang, J., Huang, L., Mou, C., Zhang, E., Wang, Y., Cao, Y., & Yang, Q. (2019) · Bioscience Reports · doi:10.1042/bsr20182028 · Cited by 42 · see citing works
Feline chronic gingivostomatitis: current concepts in clinical management
Soltero‐Rivera, M. M., Goldschmidt, S. L., & Arzi, B. (2023) · Journal of Feline Medicine and Surgery · doi:10.1177/1098612x231186834 · Cited by 41 · see citing works
Microbiota in cerebrovascular disease: A key player and future therapeutic target
Tonomura, S., Ihara, M., & Friedland, R. P. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20918031 · Cited by 40 · see citing works
“Intraepithelial lymphocytes, especially regulatory T cells, respond to antigens presented with major histocompatibility complex molecules and express tolllike receptors (TLRs); they also eliminate foreign antigens and exhibit surveillance functions in both the GI tract and oral cavity.(12) 3.”
BackgroundOh, Y., Cha, H., Hwang, S. J., Kim, D. S., Choi, Y.-J., Kim, Y., Shin, Y., Nguyen, T. T., Choi, S., Lee, J. M., et al. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-021-00964-z · Cited by 41 · see citing works
MicroRNAs associated with inflammation in shoulder tendinopathy and glenohumeral arthritis
Thankam, F. G., Boosani, C. S., Dilisio, M. F., & Agrawal, D. K. (2017) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-017-3097-7 · Cited by 40 · see citing works
“hsa-miR-23b-3p is multifunctional and regulates pathways mediating cell proliferation, adhesion, differentiation, and apoptosis [38, 39].”
BackgroundThe Role of the Microbiome in Driving RA-Related Autoimmunity
Rooney, C. M., Mankia, K. S., & Emery, P. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.538130 · Cited by 40 · see citing works
Lin, W., Kuo, Y., Chen, C., Huang, Y.-F., Hsu, C., Lin, J., Liu, C., Chen, J., Hsia, K.-C., & Ho, H.-H. (2021) · Current Microbiology · doi:10.1007/s00284-021-02569-8 · Cited by 38 · see citing works
“The oral-nasal mucosa, the gateway for contacting inhaled antigens, is the frontline defense of the human immune system [1, 2].”
BackgroundBolstering Immunity through Pattern Recognition Receptors: A Unique Approach to Control Tuberculosis
Pahari, S., Kaur, G., Aqdas, M., Negi, S., Chatterjee, D., Bashir, H., Singh, S., & Agrewala, J. N. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00906 · Cited by 37 · see citing works
“It encompasses a well-compartmentalized network of cells that imparts a protective immunity and shields from invading pathogens (40).”
BackgroundSamara, P., Athanasopoulos, M., & Athanasopoulos, I. (2023) · Microorganisms · doi:10.3390/microorganisms11071624 · Cited by 36 · see citing works
“T cells, including CD4+ helper T cells and CD8+ cytotoxic T cells, play a critical role in coordinating immune responses and eliminating infected cells [27].”
BackgroundDorta-Estremera, S. M., Chin, R. L., Sierra, G., Nicholas, C., Yanamandra, A. V., Nookala, S. M. K., Yang, G., Singh, S., Curran, M. A., & Sastry, K. J. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0892 · Cited by 33 · see citing works
“It has been reported that sublingual and buccal mucosa contain a small repertoire of immune cells, but tongue-infiltrating lymphocytes have not been clearly studied after vaccination[40, 41].”
Lim, Y., Kim, H. Y., An, S., & Choi, B. (2022) · Journal of Oral Microbiology · doi:10.1080/20002297.2022.2123550 · Cited by 33 · see citing works
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The oral-gut-circulatory axis: from homeostasis to colon cancer
Tortora, S. C., Agurto, M. I. G., & Martello, L. A. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1289452 · Cited by 31 · see citing works
“The gut-associated lymphoid tissue consists of Peyer ’ s patches and isolated lymphoid follicles (Wu et al., 2014).”
BackgroundInfluentialApplications of Chitosan in Prevention and Treatment Strategies of Infectious Diseases
Sinani, G., Sessevmez, M., & Şenel, S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16091201 · Cited by 31 · see citing works
Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells
Sparano, C., Solís-Sayago, D., Zangger, N. S., Rindlisbacher, L., Hove, H. V., Vermeer, M., Westermann, F., Mussak, C., Rallo, E., Dergun, S., et al. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20240930 · Cited by 33 · see citing works
“As part of the oral-pharyngeal immune system, SG immune cells must balance pathogen defense with tolerance to harmless food antigens, which may contribute to viral persistence (Wu et al., 2014; Atyeo et al., 2024).”
Wang, H., Bai, J., Luo, Z., Fu, J., Wang, H., & Sun, Z. (2017) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2017.04.003 · Cited by 29 · see citing works
The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation
Zeng, C., Shao, Z., Wei, Z., Yao, J., Wang, W., Yin, L., YangOu, H., & Xiong, D. (2021) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00249-w · Cited by 27 · see citing works
Medication-Related Osteonecrosis: Why the Jawbone?
Kuehn, S., Scariot, R., & Elsalanty, M. E. (2023) · Dentistry Journal · doi:10.3390/dj11050109 · Cited by 27 · see citing works
“The oral mucosal barrier involves complex immune system components that constantly recognize and eliminate harmful exogenous organisms while maintaining commensals [101].”
BackgroundClinical and Histopathologic Characterization of Canine Chronic Ulcerative Stomatitis
Anderson, J. G., Peralta, S., Kol, A., Kass, P. H., & Murphy, B. G. (2017) · Veterinary Pathology · doi:10.1177/0300985816688754 · Cited by 26 · see citing works
“The importance of T-cell diversity in the mucosal immune system of the oral cavity has been documented in humans.(60) A recent review details regulatory T cells and their role in animal diseases.”
BackgroundDanger signals in oral cavity-related diseases
Kay, J. G., Kramer, J. M., & Visser, M. B. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.4mir1118-439r · Cited by 24 · see citing works
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Sabino, J., Tarassishin, L., Eisele, C. D., Hawkins, K. A., Barré, A., Nair, N. K., Rendon, A. P., Debebe, A., Picker, M., Agrawal, M., et al. (2023) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjad096 · Cited by 23 · see citing works
Zhang, D., Wang, J., Li, Z., Zhou, M., Chen, Q., Zeng, X. Y., & Chen, Y. (2015) · Inflammation · doi:10.1007/s10753-015-0145-x · Cited by 23 · see citing works
“epithelium basal layer [2].”
BackgroundSelf-citationOral Helicobacter pylori: Interactions with host and microbial flora of the oral cavity
Krzyżek, P., & Gościniak, G. (2018) · Dental and Medical Problems · doi:10.17219/dmp/81259 · Cited by 22 · see citing works
The Role of Genistein in Mammalian Reproduction
Guelfi, G., Pasquariello, R., Anipchenko, P., Capaccia, C., Pennarossa, G., Brevini, T. A. L., Gandolfi, F., Zerani, M., & Maranesi, M. (2023) · Molecules · doi:10.3390/molecules28217436 · Cited by 22 · see citing works
“A high number of studies have demonstrated that fl avonoids are metabolized and bioactivated already in the oral phase of digestion through oral microbiome β -glucosidase activity, producing health e ff ects in the oral cavity [55,56].”
BackgroundLeukoplakia and Immunology: New Chemoprevention Landscapes?
Grigolato, R., Bizzoca, M. E., Calabrese, L. S., Leuci, S., Mignogna, M. D., & Muzio, L. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186874 · Cited by 21 · see citing works
“In general, the oral-pharyngeal mucosal immune system protects the oral cavity and the body against pathogens; it shares similar anatomical structure of other mucosal immune system [15,16].”
BackgroundZhang, E., Wang, J., Li, Y., Huang, L., Wang, Y., & Yang, Q. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8828 · Cited by 20 · see citing works
“Therefore, CD3+ T cells in the intestines serve an important role in the adaptive mucosal immune response (31).”
BackgroundAnuța, V., Talianu, M.-T., Dinu‐Pîrvu, C., Ghica, M. V., Prisada, R. M., Kaya, M. G. A., & Popa, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147520 · Cited by 20 · see citing works
Bijelić, B., Matić, I. Z., Besu, I., Janković, L., Juranić, Z. D., Marušić, S., & Andrejević, S. (2018) · Immunobiology · doi:10.1016/j.imbio.2018.10.006 · Cited by 18 · see citing works
Shen, Y., Hu, Y., & Qiu, L. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.02.012 · Cited by 18 · see citing works
Zafar, S., Rana, S. J., Sayed, E., Chohan, T. A., Küçük, İ., Nazari, K., Arshad, M. S., & Ahmad, Z. (2024) · Biomaterials Advances · doi:10.1016/j.bioadv.2024.213995 · Cited by 17 · see citing works
Jeican, I. I., Gheban, D., Barbu–Tudoran, L., Inișca, P., Albu, C., Ilieș, M., Albu, S., Vică, M. L., Matei, H. V., Tripon, S. C., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10184110 · Cited by 17 · see citing works
“Certainly, there is a complex crosstalk between immune cells residing in mucosal compartments: dendritic cells and macrophages are sentinel cells for the invading agents, T cells attack and eliminate pathogenic agents, and B cells secrete IgA [68,69].”
BackgroundUnderstanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity
Biswas, M., Nurunnabi, M., & Khatun, Z. (2024) · ACS Applied Bio Materials · doi:10.1021/acsabm.4c00395 · Cited by 16 · see citing works
de Albuquerque, J. B., dos Santos, D. S., Stein, J. V., & de Meis, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01734 · Cited by 16 · see citing works
“The oral cavity contains distinct mucosal surfaces and molecules expression, such as mucins, in which microorganisms can bind and, consequently colonize this anatomical region (57).”
BackgroundIvanova, N. A., Sotirova, Y., Gavrailov, G., Nikolova, K. T., & Andonova, V. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030530 · Cited by 15 · see citing works
“The nasal route stands out as one of the most prospective sites for peptide and protein delivery [195], and direct brain drug delivery (via the olfactory bulb) [196,197]; the buccal route reveals opportunities for sustained drug delivery, and the sublingual route allows fast access to the systemic circulation [198,199…”
BackgroundHori, H., Izawa, S., Yoshida, F., Kunugi, H., Kim, Y., Mizukami, S., Inoue, Y., Tagaya, H., & Hakamata, Y. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.01.020 · Cited by 15 · see citing works
Regulatory T cell therapy suppresses inflammation of oral mucosa
Xue, N., Wang, Y., Cheng, H., Liang, H., Fan, X., Zuo, F., Zeng, X. Y., Ji, N., & Chen, Q. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1009742 · Cited by 14 · see citing works
“The majority of oral mucosal diseases are inflammatory diseases (1).”
BackgroundSelf-citationWang, H., Jiang, Y., Wang, H., Luo, Z., Wang, Y., & Guan, X. (2018) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2018.11.015 · Cited by 14 · see citing works
Prognostic Role of Combined EGFR and Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma
Wongpattaraworakul, W., Gibson-Corley, K. N., Choi, A. B., Buchakjian, M. R., Lanzel, E. A., Rajan, A., & Simons, A. L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.885236 · Cited by 14 · see citing works
“It is possible that the tongue (and tumors derived from the tongue) are T cell rich due to the abundance of T-cells residing in the mucosa that normally control mucosal immunity and tolerance (64).”
BackgroundMucosal anti-infections vaccines: Beyond conventional vaccines
Sánchez‐Ramón, S., Manzanares, M., & Candelas, G. (2019) · Reumatología Clínica (English Edition) · doi:10.1016/j.reumae.2018.10.020 · Cited by 14 · see citing works
Decoding the microbial blueprint of pancreatic cancer
Bautista, J., Bedón-Galarza, R., Martínez-Hidalgo, F., Masache-Cruz, M. J., Benítez-Núñez, M., Valencia-Arroyo, C., & López‐Cortés, A. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1737582 · Cited by 13 · see citing works
“Constantly exposed to exogenous microorganisms through breathing, eating, and drinking, the oral cavity functions as a dynamic interface between host immunity and the external environment (84).”
Oral mucosa immunity: ultimate strategy to stop spreading of pandemic viruses
Jang, H., Matsuoka, M., & Freire, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1220610 · Cited by 13 · see citing works
Cecchin-Albertoni, C., Deny, O., Planat‐Benard, V., Guissard, C., Paupert, J., Vaysse, F., Marty, M., Casteilla, L., Monsarrat, P., & Kémoun, P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102360 · Cited by 13 · see citing works
“These exposures allow the immune oral system to interact with and respond to the diversity of microorganisms (Wu et al., 2014).”
BackgroundRecent strategies driving oral biologic administration
Alotaibi, B. S., Buabeid, M. A., Ibrahim, N. A., Kharaba, Z. J., Ijaz, M., & Murtaza, G. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1990044 · Cited by 13 · see citing works
Jacques, C., Chatelais, M., Fekir, K., Fauconnier, L., Mellier, M., Togbe, D., & Floris, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010110 · Cited by 13 · see citing works
da Cunha, A., Michelin, M. A., & Murta, E. F. C. (2016) · Immunology Letters · doi:10.1016/j.imlet.2016.07.009 · Cited by 13 · see citing works
The Role of Dysbiotic Oral Microbiota in Cardiometabolic Diseases: A Narrative Review
Lê, S., Cecchin-Albertoni, C., Thomas, C., Kémoun, P., Minty, M., & Blasco‐Baqué, V. (2023) · Diagnostics · doi:10.3390/diagnostics13203184 · Cited by 13 · see citing works
“However, in susceptible individuals, certain factors such as genetics, epigenetics, aging, lifestyle, and environmental factors can disrupt the host–microbiota homeostasis, leading to dysbiosis and to a shift toward a pathogenic microbiota [19].”
BackgroundShephard, A., Mahmood, H., Raza, S. E. A., Khurram, S. A., & Rajpoot, N. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02916-z · Cited by 11 · see citing works
“They are found in the skin and within the epithelial layer lining the intestine, lungs, reproductive tract and oral cavity, and are typically thought to be T lymphocytes [30, 31].”
Allergy Treatment: A Comprehensive Review of Nanoparticle-based Allergen Immunotherapy
Abo‐Zaid, M. A., Elsapagh, R. M., Sultan, N. S., Mawkili, W., Hegazy, M. M., & Ismail, A. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl26550 · Cited by 11 · see citing works
“The presence of mucosa-associated lymphoid tissue (MALT) and the unique environment of the oral cavity play significant roles in developing oral tolerance [84,85].”
Jacques, C., & Floris, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021483 · Cited by 12 · see citing works
“Oromucosal administration is intended to reach the numerous immune cells in the oral–pharyngeal mucosal and gastrointestinal tracts [76,77], which communicate in a continuous cross-talk with the systemic immune system [78].”
BackgroundHow Intraday Index Changes Influence Periodontal Assessment: A Preliminary Study
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“However, outside of dental circles, little attention has been paid to this fact until now [24] or to the 45% overlap of microbes found both in the mouth and in the colon [25].”
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“Their oromucosal use can allow optimization of the delivery of the active substances to the lymphoid tissues of the buccal mucosae, and to the immune cells present in the oral cavity [31,32].”
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Dietary nucleic acids promote oral tolerance through innate sensing pathways in mice
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Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies
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“M-cell-like cells have been identified in the epithelium of palatine tonsil crypts [21].”
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Dendritic Cell-Based Immunity: Screening of Dendritic Cell Subsets in Breast Cancer-Bearing Mice
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Comparative study on serum‐induced arthritis in the temporomandibular and limb joint of mice
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Immunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach
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“50,51].”
Potential applications and mechanisms of natural products in mucosal-related diseases
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“OLP is a chronic in fl ammatory disease characterized by massive lymphocyte in fi ltration in the LP and chronic destruction of the epithelial basal layer (124 – 126).”
InfluentialUnderstanding the Relationship of the Human Bacteriome with COVID-19 Severity and Recovery
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“It spans various organ systems including the gastrointestinal tract (GIT) and the respiratory tract, to name a few [34].”
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“The present study focused on investigating the effect of changes intheoralmicrobiotacommunitycompositiononthediverseimmune responses to ART in PLWH.”
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Identification and Regulation of TCRαβ+CD8αα+ Intraepithelial Lymphocytes in Murine Oral Mucosa
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“TCRβCD8αα IELs Reside in Oral Mucosa TCRβCD8αα IELs in the gut represent in the frontal lining of the mucosal immune system to maintain immune homeostasis (1, 4, 21).”
BackgroundInfluentialSelf-citationThe role of the oral microbiota in allergic diseases: Current understandings and future trends
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- Authors
- Wu, R.-Q., Zhang, D.-F., Tu, E., Chen, Q.-M., & Chen, W.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Chen, WanJun
- ORCID
- Venue
- International Journal of Oral Science
- Published
- 2014-08-08
- Volume
- 6
- Issue
- 3
- Pages
- 125-132
- ISSN
- 1674-2818 (ISSN-L)
- 2049-3169
- PMC
- PMC4170154
- OpenAlex
- W2005120878
- Cited by
- 171
- References
- 101
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 23 · 2023: 21 · 2022: 16 · 2021: 19 · 2020: 16 · 2019: 11 · 2018: 17 · 2017: 11 · 2016: 2 · 2015: 5
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Oral Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (2012DFA31370, 81321002)
- National Institutes of Health
- National Institute of Dental and Craniofacial Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- oral mucosal immunity, T cell subsets, T cell diversity, immune homeostasis, commensal microorganisms, pathogen defense, immune barrier, signaling proteins
- MeSH terms
- Epithelium, Humans, Immunity, Cellular, Mouth Diseases, Mouth Mucosa, Pharynx, T-Lymphocyte Subsets, Immunity, Mucosal
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