연구분야

Interaction between Bacteria and Immune System in the Oral Cavity

The human oral cavity carries a microbial community composed of hundreds of bacterial species. Most of them are commensals and only some are associated with dental caries, gingivitis, periodontitis, periapical infection, and endocarditis. Immune components that confront these bacteria in oral cavity include epithelial barrier, neutrophils, mast cells, dendritic cells, T cells, macrophages, and salivary antimicrobial molecules. We are interested in the interaction between our immune system and oral bacteria in health and disease

Pathogenesis ofPeriodontitis

The major focuses of research are the pathogenesis of periodontitis and immune modulation to prevent periodontitis. Periodontitis can be defined as the inflammation of periodontal tissue caused by subginigival plaque bacteria, leading to tissue destruction. Only 10% of elderly population inKorea maintains healthy periodontium, calling our attention to this disease. We have our own model for the pathogenesis of periodontitis: breach in the defense mechanisms against plaque bacteria in gingival sulcus results in persistent infection with invasive bacteria, which lead to chronic inflammation and tissue destruction. Based on this model, several clinical studies are ongoing.

Basic Immunology

 We are also addressing basic immunological questions in relation to immune responses to oral bacteria. Oral mucosal epithelium is in constant contact with numerous bacteria but inflammation is not normally seen in the oral mucosa. How the immune tolerance to commensal bacteria is regulated is not known at all. Therefore, the pattern recognition receptors of oral epithelial cells involved in the recognition or ignorance of bacteria are important. In general, mucosal epithelia not only form a protective barrier, but also initiate immune responses by secreting various cytokines and chemokines. The barrier function of epithelia is attributed to the unique architectural integrity and production of antimicrobial peptides. We are dissecting the pattern recognition receptors of oral epithelial cells that mediate induction of antimicrobial peptides, inflammatory cytokines, and chemokines. We previously examined that several oral bacterial species are highly susceptible to non-opsonic phagocytosis by human neutrophils. Neutrophils are important phagocytes that first arrive in the infection sites; however, receptors involved in non-opsonic phagocytosis have been poorly characterized. Identification and characterization of non-opsonic phagocytic receptors is underway. Another interesting question we are addressing is whether or not healthy people have specific T cell response to commensal oral bacteria. Our ultimate goal of research is to modulate immune responses in the oral cavity to prevent oral diseases.

Ongoing Projects and Future Direction

▶ Clinical Study

▷ Comparison of neutrophil function in healthy individuals vs. patients with periodontitis

▷  Bacterial Ag-speicific T cell response in healthy individuals vs. patients with periodontitis

▷  The level of IGF-1 and IGFBP-3 in GCF and plasma in healthy individuals vs. patients with periodontitis

▷ Epithelial barrier function and bacterial invasion in healthy individuals vs. patients with periodontitis

▶ Basic Immunology

▷ Dissect the pattern recognition receptors of oral epithelial cells that mediate IL-8, TNFa, or IL-1a induction.

▷ Molecular mechanisms for the suppressive effect of Treponema denticola on epithelial cell immune responses

▷ Characterization of non-opsonic phagocytic receptors in human neutrophils

▶  Immune Modulation

▷ Modulation of neutrophil phagocytic function

▷ Modulation of epithelial barrier function

연구업적

SCI Papers

 1. Beers T, Du T-L, Rickert M, Overturf P, Choi Y, Greenberg SJ. Ex vivo clonotype primer-directed gene amplification to identify malignant T cell repertoires. J. Leukocyte Biol. 54:343-350, 1993.

 2. Greenberg SJ, Choi Y, Ballow M, Du T-L, Ward P, Rickert MH, Frankel S, Bernstein S, Brecher M. Profile of immunoglobulin heavy chain variable gene repertoires and highly selective detection of malignant clonotypes in acute lymphoblastic leukemia. J. Leukocyte Biol. 57: 856-864, 1995.

 3. Choi Y, Rickert MH, Ballow M, Greenberg SJ. Human IgH-V gene repertoire in neonatal cord blood, adult peripheral blood and EBV-transformed cells. Ann. NY. Acad. Sci. 764: 553-555, 1995.

 4. Choi Y, Du T-L, Ward P, Overturf P, Brecher M, Ballow M, Greenberg SJ. Clonal evolution in B-lineage acute lymphoblastic leukemia by contemporaneous V_H-V_H gene replacements and V_H-DJ_H gene rearrangements. Blood 87: 2506-2512, 1996.

 5. Yoshida M, Rachel JR, Choi Y, Greenberg SJ, Barcos M, Kawata A, Matsuno F, Seon BK. Development of a SCID mouse model consisting of highly disseminated human B cell leukemia/lymphoma, cure of the tumors by systemic administration of immunotoxin, and development/application of a clonotype-specific PCR-based assay. Cancer Research 57: 678-685, 1997.

 6. Sneller MC, Wang J, Dale JK, Strober W, Middelton LA, Choi Y, Fleisher TA, Lim MS, Jaffe ES, Puck JM, Lenardo MJ, Straus SE. Clinical, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Blood. 89: 1341-1348, 1997.

 7. Jackson CE, Fischer RE, Hsu AP, Anderson SM, Choi Y, Wang J, Dale JK, Fleisher TA, Middelton LA, Sneller MC, Lenardo MJ, Straus SE, Puck JM. Autoimmune lymphoproliferative syndrome with Defective Fas: Genotype influences Penetrance. Am J Hum Genet. 64: 1002-1014, 1998.

 8. Choi Y, Ramnath VR, Eaton AS, Chen A, Simon-Stoos KL, Kleiner DE, Erikson J, Puck JM. Expression in transgenic mice of dominant interfering Fas mutations: A model for human autoimmune lymphoproliferative syndrome. Clin Immunol. 93: 34-45, 1999.

 9. Choi Y, Woo KM, Ko S-H, Lee YJ, Park S-J, Kim H-M, Kwon BS. Osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8+ T cells. Eur J Immunol. 31: 2179-2188, 2001.

 10. Choi Y, Simon-Stoos K, Puck JM. Hypo-active variant of IL-2 and associated decreased T-cell activation contribute to impaired apoptosis in autoimmune prone MRL mice. Eur J Immunol. 32: 677-684, 2002.

 11. Woo KM, Choi Y, Ko S-H, Ko JS, Oh K-O, Kim KK. Osteoprotegerin is present on the membrane of osteoclasts isolated from mouse long bones. Exp Mol Med. 34: 347-352, 2002.

 12. Choi Y Kim JJ. B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis. Exp Mol Med. 35: 385-392, 2003.

 13. Chang S-H, Sung H-C, Choi Y, Ko S-Y, Lee B-E, Back D-H, Kim S-W, Kim J-K. Suppressive Effect of AIF, a water extract of three herb, on collagen-induced arthritis in mice. Int Immunopharmacol. 5:1365-1372, 2005.

 14. Park H, Jung Y-K, Park O-J, Lee YJ, Choi J-Y, Choi Y. Interaction of Fas ligand (FasL) and Fas expressed on osteoclast precursors increases osteoclastogenesis. J Immunol. 175: 7193-7201, 2005.

 15. Park H, Park O-J, Shin J, Choi Y. Receptor activator of NF-kB ligand enhances the activity of macrophages as antigen presenting cells. Exp Mol Med. 37: 524-532, 2005.

 16. Kim HA, Kim S, Chang SH, Hwang HJ, Choi Y. Anti-arthritic effect of ginsenoside Rb1 on collagen induced arthritis in mice Int Immunopharmacol. 7: 1286-1291, 2007.

 17. Ji S, Hyun J, Park E, Lee B-L, Kim K-K, Choi Y. Susceptibility of Various Oral Bacteria to Antimicrobial Peptides and to Pagosytosis by Neutrophils. J Periodontal Res. 42: 410-419, 2007.

 18. Ji S, Kim YS, Min B-M, Han SH, Choi Y. Innate Immune Responses of Gingival Epithelial Cells to Non-periodontopathic and Periodontopathic Bacteria. J Periodontal Res. 42: 503-510, 2007.

 19. S Chang, Choi Y, Hwang H-J, Jung D-S, Shin J, Yang J-H, Ko S-Y, Kim S-W, Kim J-K. Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model. Clinical Nutrition. 26: 785-791, 2007.

 20. Shin JE, Ji S, Choi Y. Ability of Oral Bacteria to Induce Tissue-destructive Molecules from Human Neutrophils. Oral Diseases. 14: 327-334, 2008.

 21. Yang  J, Park OJ, Lee YJ, Jung H-M, Woo KM, Choi Y. 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling. Eur J Immunol. 38: 1598-1609, 2008.

 22. Park O-J, Shin S-Y, Choi Y, Kim M-H, Chung C-P, Ku Y, Kim K-K. The Association of Osteoprotegerin Gene Polymorphisms with Periodontitis. Oral Diseases. 14: 440-444, 2008.

 23. Ji S, Shin JE, Kim YS, Oh J-E, Min B-M, Choi Y. TLR2 and NALP2 mediate induction of human beta-defensins by Fusobacterium nucleatum in gingival epithelial cells. Infect Immun. 77: 1044-1052, 2009.

 24. Kurokawa K, Lee H, Roh KB, Asanuma M, Kim YS, Nakyama H, Shiratsuchi A, Choi Y, Takeuchi O, Kang HJ, Dohmae N, Nakanishi Y, Akira S, Sekimizu K, Lee BL. The triacylated ATP binding cluster transporter substrate-binding lipoprotein of Staphylococcus aureus functions as a native ligand for the toll-like receptor 2. J Biol Chem. 284: 8406-8411, 2009

 25. Shin JE, Kim YS, Oh J-E, Min B-M, Choi Y. Treponema denticola suppresses expression of human beta-defensin-3 in gingival epithelial cells through inhibition of TLR2 activation axis. Infet Immun. 78: 672-679, 2010.

 26. Chun J, Kim KY, Lee J-H, and Choi Y. Pyrosequencing Analysis of Murine Oral Microbial Communities. BMC Microbiology. 10: 101, 2010

 27. Shin JE, Choi Y. Treponema denticola suppresses expression of human beta-defensin-2 in gingival epithelial cells through inhibition of TNFaproduction and TLR2 activation. Molecules and Cells. 29: 407-412, 2010.

 28. Kim YC, Ko Y, Hong S-D, Kim KY, Lee YH, Chae C, Choi Y. Presence of Porphyromonas gingivalis and Plasma Cell Dominance in Gingival Tissues with Periodontitis. Oral Diseases. 16: 375-381, 2010.

 Non-SCI Papers

 1. Lee S-J, Lim Y-H, Choi Y, Kim H-R and Cheong D-K. The effect of morphine and its antagonist microinjected into nucleus raphe magnus on the release of serotonin into spinal cord superfusates of the rat. The Korean J. Oral Biol. 15: 63, 1991.

 2. Kim JJ, Lee BE, Jung DS, Kim S-W, Ko S-Y, Baek D-H, Chang S-H, Choi Y. Immunoregulatory effects of extracts from the stem bark of Albizzia julibrissin Durazz. Int. J. Oral Biol. 29: 137-144, 2004.

 3. Ji S, Lee J-O, Choi Y. Measurement of bacterial (E. coli) concentration by flow cytometry. Int. J. Oral Biol. 30: 65-69, 2005.

 4. Kim Y, Ji S, Junc H-M, Woo KM, and Choi Y. Induction of Bone Morphogenetic Protein-2 from Gingival Epithelial Cells by Oral Bacteria. Int. J. Oral Biol. 32: 103-108, 2007.

 5. Shin JE, Ji S, Choi Y. Expression of Various Pattern Recognition Receptors in Gingival Epithelial Cells. Int. J. Oral Biol. 33: 77-82, 2008.

 6. Choi Y, Lee J, Hong SD, Cuburu N, Czerkinsky C. Distribution of Immune Cells within Human Sublingual Mucosa. Int. J. Oral Biol. 34: 131-135, 2009.