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A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17
Open accessAbstract
For almost two decades, the Th1/Th2 paradigm has offered a productive conceptual framework for investigating the pathogenesis of periodontitis. However, as with many other inflammatory diseases, the observed role of T-cell-mediated immunity in periodontitis did not readily fit this model. A new subset of CD4+ T-cells was recently discovered that explains many of the discrepancies in the classic Th1/Th2 model, and has been termed “Th17” based on its secretion of the novel pro-inflammatory cytokine IL-17. The identification of Th17 cells as a novel effector T-cell population compels re-examination of periodontitis in the context of the new subset and its signature cytokines. This review aims to offer a clarifying insight into periodontal pathogenesis under the extended Th1/Th2/Th17 paradigm, and is predicated on the principle that periodontal disease activity is determined by a complex interplay between the immune system and periodontal pathogens. The re-examination of existing periodontal literature and further studies in the light of these new discoveries may help explain how the inflammatory response results in damage to the periodontium while generally failing to control the pathogens. This knowledge is essential for the development of immunomodulatory intervention strategies for fine-tuning the host response to maximize the protective and minimize the destructive aspects of the periodontal host response. Moreover, with the advent of anti-cytokine biologic drugs that target the Th1 and Th17 pathways in autoimmunity, the potential consequences to periodontal disease susceptibility in humans need to be understood.
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“IL-17, produced primarily by CD4+ Th17 cells, acts to enhance chemokine production by target cells in various tissues to promote/attract monocytes and neutrophils to those tissue (especially mucosal) sites, and in combination with sICAM suggests the predominance of a Th1 phenotypic response (acute pro-inflammatory state) [25-30].”
From Oral neutrophils are an independent marker of the systemic inflammatory response after cardiac bypass (2014) · cites this paper as [25]
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“This increased expression of adhesion molecules stimulates the trans-endothelial migration of neutrophils) [25-29].”
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“IL-17 promotes endothelial activation by inducing the expression of endothelial adhesion markers (E-selectin, VCAM-1, and ICAM-1) in a p38 MAPK-dependent manner.”
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Metadata
- Authors
- Gaffen, S. L., & Hajishengallis, G.
- Affiliations
- University of Louisville (US)
- Corresponding author
- Gaffen, S.L.
- Venue
- Journal of Dental Research
- Publisher
- SAGE Publications
- Published
- 2008-09
- Volume
- 87
- Issue
- 9
- Pages
- 817-828
- ISSN
- 0022-0345 (ISSN-L)
- 1544-0591
- PMC
- PMC2692983
- OpenAlex
- W2036608242
- Cited by
- 334
- References
- 171
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 14 · 2023: 11 · 2022: 8 · 2021: 17 · 2020: 18 · 2019: 22 · 2018: 14 · 2017: 24 · 2016: 19 · 2015: 20 · 2014: 27 · 2013: 29 · 2012: 25
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Dental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R21AI049329, AI49329, R01AI049329)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR054389, R01AR054389)
- National Institute of Dental and Craniofacial Research (R01DE018292, DE-015254, DE017138, R01DE015254, DE018292, R01DE017138)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Keywords
- periodontitis, Th1/Th2 paradigm, Th17 cells, IL-17, CD4+ T cells, periodontal disease pathogenesis, T cell immunity, host-pathogen interaction, periodontal pathogens, immunomodulatory therapy, periodontal disease susceptibility
- MeSH terms
- Animals, Humans, Immunity, Cellular, Interleukins, Periodontitis, T-Lymphocyte Subsets, Th1 Cells, Th2 Cells, Models, Immunological, Interleukin-17
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