The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Revisiting the Page & Schroeder model: the good, the bad and the unknowns in the periodontal host response 40 years later
Open accessAbstract
In their classic 1976 paper, Page & Schroeder described the histopathologic events and the types of myeloid cells and lymphocytes involved in the initiation and progression of inflammatory periodontal disease. The staging of periodontal disease pathogenesis as ‘initial’, ‘early’, ‘established’ and ‘advanced’ lesions productively guided subsequent research in the field and remains fundamentally valid. However, major advances regarding the cellular and molecular mechanisms underlying the induction, regulation and effector functions of immune and inflammatory responses necessitate a reassessment of their work and its integration with emerging new concepts. We now know that each type of leukocyte is actually represented by functionally distinct subsets with different, or even conflicting, roles in immunity and inflammation. Unexpectedly, neutrophils, traditionally regarded as merely antimicrobial effectors in acute conditions and protagonists of the ‘initial’ lesion, are currently appreciated for their functional versatility and critical roles in chronic inflammation. Moreover, an entirely new field of study, osteoimmunology, has emerged and sheds light on the impact of immunoinflammatory events on the skeletal system. These developments and the molecular dissection of crosstalk interactions between innate and adaptive leukocytes, as well as between the immune system and local homeostatic mechanisms, offer a more nuanced understanding of the host response in periodontitis, with profound implications for treatment. At the same time, deeper insights have generated new questions, many of which remain unanswered. In this review, 40 years after Page & Schroeder proposed their model, we summarize enduring and emerging advances in periodontal disease pathogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · cited 2×
“In fact, the M1 and M2 subsets represent extremes of a continuum of different activation states (184, 190, 255).”
BackgroundMacrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Neutrophil recruitment and function in health and inflammation
Kolaczkowska, E., & Kubes, P. (2013) · Nature Reviews Immunology · doi:10.1038/nri3399 · Cited by 5,472
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873
Complement: a key system for immune surveillance and homeostasis
Ricklin, D., Hajishengallis, G., Yang, K., & Lambris, J. D. (2010) · Nature Immunology · doi:10.1038/ni.1923 · Cited by 3,654 · cited 1×
“Also in recent years, complement started to be appreciated as a central system of immune surveillance and homeostasis and a key link between innate and adaptive immunity (228).”
BackgroundSelf-citationDewhirst, F. E., Chen, T., Izard, J., Paster, B. J., Tanner, A. C. R., Yu, W.-H., Lakshmanan, A., & Wade, W. G. (2010) · Journal of Bacteriology · doi:10.1128/jb.00542-10 · Cited by 3,352
Periodontitis: from microbial immune subversion to systemic inflammation
Hajishengallis, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3785 · Cited by 3,046
Self-citationResolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862
Liang, S. C., Tan, X.-Y., Luxenberg, D. P., Karim, R., Dunussi-Joannopoulos, K., Collins, M., & Fouser, L. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061308 · Cited by 2,330
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130
Complement and its role in innate and adaptive immune responses
Dunkelberger, J. R., & Song, W.-C. (2010) · Cell Research · doi:10.1038/cr.2009.139 · Cited by 1,932
The history of toll-like receptors - redefining innate immunity
O'Neill, L. A. J., Golenbock, D., & Bowie, A. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3446 · Cited by 1,765
Targeting IL-17 and TH17 cells in chronic inflammation
Miossec, P., & Kolls, J. K. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3794 · Cited by 1,414
Alveolar macrophages: plasticity in a tissue-specific context
Hussell, T., & Bell, T. J. (2014) · Nature Reviews Immunology · doi:10.1038/nri3600 · Cited by 1,377
The multifaceted functions of neutrophils
Mayadas, T. N., Cullere, X., & Lowell, C. A. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164023 · Cited by 1,356
Functional Specialization of Interleukin-17 Family Members
Iwakura, Y., Ishigame, H., Saijo, S., & Nakae, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.012 · Cited by 1,289
Hajishengallis, G., Liang, S., Payne, M. A., Hashim, A., Jotwani, R., Eskan, M. A., McIntosh, M. L., Alsam, A., Kirkwood, K. L., Lambris, J. D., et al. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.006 · Cited by 1,154
Self-citationHow leukocytes cross the vascular endothelium
Vestweber, D. (2015) · Nature Reviews Immunology · doi:10.1038/nri3908 · Cited by 858
γδ T cells: functional plasticity and heterogeneity
Carding, S. R., & Egan, P. J. (2002) · Nature Reviews Immunology · doi:10.1038/nri797 · Cited by 814
Ocular immune privilege: therapeutic opportunities from an experiment of nature
Streilein, J. W. (2003) · Nature Reviews Immunology · doi:10.1038/nri1224 · Cited by 807
Molecular aspects of the pathogenesis of periodontitis
Meyle, J., & Chapple, I. (2015) · Periodontology 2000 · doi:10.1111/prd.12104 · Cited by 705
Stress, Inflammation, and Defense of Homeostasis
Chovatiya, R., & Medzhitov, R. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.030 · Cited by 704
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622
Polymicrobial synergy and dysbiosis in inflammatory disease
Lamont, R. J., & Hajishengallis, G. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.004 · Cited by 585 · cited 2×
“Recent microbiome and mechanistic studies revealed that: (i) the periodontitis-associated microbiota is much more diverse and complex than traditionally thought; and (ii) its role in disease involves polymicrobial synergistic and dysbiotic interactions with the host (4, 49, 52, 90, 143).”
BackgroundSelf-citationProinflammatory T helper type 17 cells are effective B-cell helpers
Mitsdoerffer, M., Lee, Y., Jäger, A., Kim, H.-J., Korn, T., Kolls, J. K., Cantor, H., Bettelli, E., & Kuchroo, V. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009234107 · Cited by 534
The Junctional Epithelium: from Health to Disease
Bosshardt, D. D., & Lang, N. P. (2005) · Journal of Dental Research · doi:10.1177/154405910508400102 · Cited by 388
Gaffen, S. L., & Hajishengallis, G. (2008) · Journal of Dental Research · doi:10.1177/154405910808700908 · Cited by 334
Self-citationCommunity-wide transcriptome of the oral microbiome in subjects with and without periodontitis
Duran-Pinedo, A. E., Chen, T., Teles, R., Starr, J. R., Wang, X., Krishnan, K., & Frias-Lopez, J. (2014) · The ISME Journal · doi:10.1038/ismej.2014.23 · Cited by 327 · cited 1×
“Recent microbiome and mechanistic studies revealed that: (i) the periodontitis-associated microbiota is much more diverse and complex than traditionally thought; and (ii) its role in disease involves polymicrobial synergistic and dysbiotic interactions with the host (4, 49, 52, 90, 143).”
BackgroundHajishengallis, G., & Lamont, R. J. (2016) · Trends in Microbiology · doi:10.1016/j.tim.2016.02.010 · Cited by 275 · cited 2×
“This may be related to the very nature of periodontal disease, a polymicrobial community-induced dysbiotic malady (88), in which a potentially protective antimicrobial response could be offset by bystander tissue damage.”
BackgroundSelf-citationComparison of neutrophil functions in aggressive and chronic periodontitis
Ryder, M. I. (2010) · Periodontology 2000 · doi:10.1111/j.1600-0757.2009.00327.x · Cited by 199
Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages
Stout, R. D., Watkins, S. K., & Suttles, J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0209073 · Cited by 183
Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States
Fine, N., Hassanpour, S., Borenstein, A., Sima, C., Oveisi, M., Scholey, J., Cherney, D., & Glogauer, M. (2016) · Journal of Dental Research · doi:10.1177/0022034516645564 · Cited by 163
Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease
Landzberg, M., Doering, H., Aboodi, G. M., Tenenbaum, H. C., & Glogauer, M. (2015) · Journal of Periodontal Research · doi:10.1111/jre.12211 · Cited by 147
Mohamed, S. G.-K., Sugiyama, E., Shinoda, K., Taki, H., Hounoki, H., Abdel-Aziz, H. O., Maruyama, M., Kobayashi, M., Ogawa, H., & Miyahara, T. (2007) · Bone · doi:10.1016/j.bone.2007.05.016 · Cited by 120
Cited by
Periodontitis: facts, fallacies and the future
Slots, J. (2017) · Periodontology 2000 · doi:10.1111/prd.12221 · Cited by 1,153
The cytokine network involved in the host immune response to periodontitis
Pan, W., Wang, Q., & Chen, Q. (2019) · International Journal of Oral Science · doi:10.1038/s41368-019-0064-z · Cited by 696
Current understanding of periodontal disease pathogenesis and targets for host‐modulation therapy
Hajishengallis, G., Chavakis, T., & Lambris, J. D. (2020) · Periodontology 2000 · doi:10.1111/prd.12331 · Cited by 502
Self-citationThe Nexus Between Periodontal Inflammation and Dysbiosis
Van Dyke, T. E., Bartold, P. M., & Reynolds, E. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00511 · Cited by 458
Biosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases
Steigmann, L., Maekawa, S., Sima, C., Travan, S., Wang, C.-W., & Giannobile, W. V. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.588480 · Cited by 77
Metadata
- Authors
- Hajishengallis, G., & Korostoff, J. M.
- Venue
- Periodontology 2000
- Publisher
- Wiley
- Published
- 2017-07-31
- Volume
- 75
- Issue
- 1
- Pages
- 116-151
- ISSN
- 0906-6713 (ISSN-L)
- 1600-0757
- OpenAlex
- W2741932595
- Cited by
- 241
- References
- 36
- FWCI
- 22.69
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.