To date we have performed a detailed histological characterization of the the cellular infiltrate in the lesion of periodontitis. Additionally we have interogated the transcriptional profile of periodontitis as compared to that of health and gingivitis and have evaluated the proteomic response in the crevicular fluid or periodontitis patients. Our results show an upregulation of immune pathways related to IL-17 responses in the context of periodontitis. Periodontitis lesions were found to be abundantly populated by IL-17 secreting cells, cells linked to infection, chronic inflammation, autoimmunity and pathology. These findings expand previous clinical studies demonstrating high levels of IL-17 cytokine in the sera and tissues of patients with periodontitis. Expression of the signature Th17 cytokine IL-17 as well as the Th17 supporting cytokines IL-1, IL-6 and IL-23 were also significantly higher in diseased lesions and tissue exudates. Finally, expression of IL-17 correlated with increased tissue damage in periodontitis. Our previous studies had indicated that the periodontal pathogen P. gingivalis can promote the upregulation of Th17 responses in vitro. We have shown that interaction of P. gingivalis with myeloid antigen presenting cells promotes Th17 differentiation. P. gingivalis stimulated production of cytokines linked to Th17 polarization, and not Th1 related cytokines. Accordingly, when supernatants from myeloid cells stimulated with P. gingivalis were added to PBMC, they supported the differentiation of T cells into Th17 but did not influence Th1 differentiation. How various microbes and their products can shape inflammatory responses in the oral cavity is of increased interest and will continue to be interogated in our program through clinical assocations and mechanists studies in vitro and in animal models.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$405,896
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
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Moutsopoulos, Niki M; Konkel, Joanne E (2018) Tissue-Specific Immunity at the Oral Mucosal Barrier. Trends Immunol 39:276-287
Konkel, J E; Moutsopoulos, N M (2018) Unique Tailoring of Th17 at the Gingival Oral Mucosal Barrier. J Dent Res 97:128-131
Dutzan, Nicolas; Abusleme, Loreto; Bridgeman, Hayley et al. (2017) On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 46:133-147
Abusleme, L; Moutsopoulos, N M (2017) IL-17: overview and role in oral immunity and microbiome. Oral Dis 23:854-865
Abusleme, Loreto; Hong, Bo-Young; Hoare, Anilei et al. (2017) Oral Microbiome Characterization in Murine Models. Bio Protoc 7:
Dutzan, Nicolas; Konkel, Joanne E; Greenwell-Wild, Teresa et al. (2016) Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol 9:1163-1172
Dutzan, Nicolas; Abusleme, Loreto; Konkel, Joanne E et al. (2016) Isolation, Characterization and Functional Examination of the Gingival Immune Cell Network. J Vis Exp :53736
Konig, Maximilian F; Abusleme, Loreto; Reinholdt, Jesper et al. (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176
Hajishengallis, George; Moutsopoulos, Niki M (2014) Etiology of leukocyte adhesion deficiency-associated periodontitis revisited: not a raging infection but a raging inflammatory response. Expert Rev Clin Immunol 10:973-5
Moutsopoulos, Niki M; Konkel, Joanne; Sarmadi, Mojgan et al. (2014) Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med 6:229ra40

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