최영님 Young-nim Choi   교수 / D.D.S. Ph.D.
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구강미생물학-면역학교실 / 면역및분자미생물치의학
· Major : 면역학
· E-mail : youngnim@snu.ac.kr
· Tel : 02-740-8643
· Laboratory : 감염-면역학 연구실
Current Research Interests

Interaction between Oral Bacteria and Immune System in the setting of Several Diseases

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 diseases. In addition to the aforementioned well-known diseases, we believe that oral bacteria have an important role in diseases of unknown etiology, such as oral lichen planus and Sjogren disease.

 

 

Pathogenesis of Oral Mucosal Diseases

The study of periodontitis taught us the importance of bacterial invasion and persistent infection in the initiation of chronic inflammation. We applyied this concept to study the pathogenesis of oral mucosal diseases with unknown etiology, such as oral lichen planus (OLP). Recently, we reported that the presence of bacteria within the epithelial cells and infiltrated T cells in OLP lesions may be the cause of T cell infiltration and the epithelial damage.  Detail pathogenesis is under investigation. 



 

Pathogenesis of Autoimmune Diseases

One of the hypotheses to explain the initiation of autoimmune diseases is molecular mimicry between microbial antigen and self antigen. We accidently found that many bacteria in environments and oral flora contain proteins that are highly conserved in human. For example, aquaporins (AQPs) are water channel proteins that are found from bacteria to human. We found that many oral bacteria have porin or aquaporins that have high homology with human AQP5, the major AQP expressed in the salivary and lacrimal glands. Actually, we identified anti-AQP5 autoantibodies in the sera from patients with Sjogren's syndrome and the presence of anti-AQP5 autoantibodies was associated with low resting salivary flow. The potential role of oral bacteria in the development of anti-AQP5 autoantibodies and Sjogren's syndrome is under investigation using cell system and animal models.

 

Specific Questions under Investigation

     1.  How antibody response is regulated against invading vs. non-invading oral bacteria?
2.  Which one is a causative bacterial species for oral lichen planus?
3.  What is the role of bacterial invasion of T cells in the pathogenesis of oral lichen planus?

4.  How germinal center B cells distinguish self- vs. foreign antigen after somatic hypermutation?
5.  Can dysbiosis of oral microbiome cause focal lymphocytic sialadenitis in Sjogren syndrome?
6.  Do nociceptive neurons have a role in anti-microbial function?

 

Research Methodology

Bacteria and cell culture

Flow cytometry

Real-time PCR

ELISA and western

Immunohistochemistry

Immunofluorescence

In situ hybridization of bacterial 16S rRNA

Analysis of microbiota by pyrosequencing

Animal models

Publication / Patent

Recent papers

 

38. Jo A, Baek KJ, Shin JE, Choi Y. Mechanisms of IL-8 suppression by Treponema denticola in gingival epithelial cells. Immunol Cell Biol. 92:139-147, 2014.

 

39. Choi YS, Kim YC, Ji S, Choi Y. Increased Bacterial Invasion and Differential Expression of Tight Junction Proteins, Growth Factors, and Growth Factor Receptors in Periodontal Lesions. J Periodontol. 85: e312-e322, 2014.

 

40. Alam J, Baek KJ, Choi YS, Kim YC, Choi Y. N-acetylcysteine and the human serum components that inhibit bacterial invasion of gingival epithelial cells prevent experimental periodontitis in mice. . J Periodontal Implant Sci. 44: 266-273, 2014.

 

41. Baek KJ, Ji S, Kim YC, Choi Y. Association of the invasion ability of Porphyromonas gingivalis with the severity of periodontitis. Virulence 6:274-281, 2015.

 

42. Choi YS, Kim YC, Baek KJ, Choi Y. In Situ Detection of Bacteria within Paraffin-embedded Tissues Using a Digoxin-labeled DNA Probe Targeting 16S rRNA. J Vis Exp. 99:e52836, 2015.

 

43. Lee HK, Ji S, Park SJ, Choung HW, Choi Y, Lee HJ, Park SY, Park JC. Odontogenic ameloblast-associated protein (ODAM) Mediates Junctional Epithelium Attachment to Tooth via Integrin-ODAM-ARHGEF5-RhoA Signaling. J Biol Chem. 290:14740-14753, 2015

 

44. Ji S, Choi YS. Point-of-care diagnosis of periodontitis using saliva: technically feasible but still a challenge. Front Cell Infect Microbiol. 5:65, 2015.

 

45. Ji S, Choi YS, Choi Y. Bacterial invasion and persistence: critical events in the pathogenesis of periodontitis? J Periodontal Res. 50:570-585, 2015.

 

46. Kim YC, Choi YS, Alam J, Kim YJ, Baek KJ, Koh J, Song YW, Chung DH, Choi Y. Induction of proteinase 3-anti-neutrophil cytoplasmic autoantibodies by proteinase 3-homologous bacterial protease in mice. Immunol Res. 64:438-444, 2016.

 

47. Kim YJ, Choi YS, Baek KJ, Yoon SH, Park HK, Choi Y. Mucosal and salivary microbiota associated with recurrent aphthous stomatitis. BMC Microbiol. 16 Suppl 1:57, 2016.

 

48. Choi YS, Kim YJ, Yoon HJ, Baek KJ, Alam J, Park HK, Choi Y The presence of bacteria within tissue provides insights into the pathogenesis of oral lichen planus. Sci Rep. 6:29186, 2016.

 

49. Alam J, Koh JH, Kim N, Kwok S-K, Park S-H, Song YW, Park K, Choi Y. Detection of autoantibodies against aquaporin 5 in the sera of patients with primary Sjögren’s syndrome. Immunol Res. 64: 845-856, 2016.

51. Baek KJ, Choi YS, Kang CK, Choi Y. The proteolytic activity of Porphyromonas gingivalis is critical in a murine model of periodontitis. Journal of Periodontology 88:218-224, 2017.
 
52. Alam J, Choi YS, Koh JH, Kwok SK, Park SH, Song YW, Park K, Choi Y. Detection of Autoantibodies against Aquaporin-1 in the Sera of Patients with Primary Sjögren's Syndrome. Immune Netw. 17:103-109, 2017.
 
53. Park J-Y, Chung H, Choi Y, Park J-H. Phenotype and Tissue Residency of Lymphocytes in the Murine Oral Mucosa. Frontiers in Immunology 8:250, 2017.
 
54. Jang JY, Song I-S, Baek KJ, Choi Y, Ji S. Immunologic characteristics of human gingival fibroblasts in response to oral bacteria. Journal of Periodontal Research 52:447-457, 2017.
 
55. Abdi K, Chen T, Klein BA, Tai AK, Coursen J, Liu X, Skinner J, Periasamy S, Choi Y, Kessler BM, Palmer RJ, Gittis A, Matzinger P, Duncan MJ, Singh NJ. Mechanisms by which Porphyromonas gingivalis evades innate immunity. PLoS One. 12:e0182164, 2017.
 
56. Namkoong E, Lee SW, Kim N, Choi Y, Park K. Effect of anti-muscarinic autoantibodies on leukocyte function in Sjögren's syndrome. Molecular Immunology 90:136-142, 2017.
 
57. Alam J, Koh JH, Kwok S-K, Park S-H, Park K, Choi Y. Functional epitopes for anti-aquaporin 5 antibodies in Sjögren’s syndrome. Journal of Dental Research 96:1414-1421, 2017.
 
58. Chang F, Kim JM, Choi Y, Park K. MTA promotes chemotaxis and chemokinesis of immune cells through distinct calcium-sensing receptor signaling pathways. Biomaterials 150:14-24, 2018.
 
59. Baek KJ, Ji S, Choi Y. Complex intra-tissue microbiota forms biofilms in periodontal lesions. Journal of Dental Research 97:192-200, 2018.
 
60. Baek KJ, Choi Y. The microbiology of oral lichen planus: Is microbial infection the cause of oral lichen planus? Molecular Oral Microbiology 33:22-28, 2018.
 
61. Lee A, Kim YC, Baek K, Alam J, Choi YS, Rheu Y, Shin YJ, Kim S, Kim HD, Song YW, Choi Y. Treponema denticola enolase contributes to the production of antibodies against ENO1 but not to the progression of periodontitis. Virulence 9:1263-1272, 2018.
 
62. Choi YS, Baek K, Choi Y. Estrogen reinforces barrier formation and protects against tumor necrosis factor alpha-induced barrier dysfunction in oral epithelial cells. J Periodontal Implant Sci. 48:284-294, 2018.
 
63. Jang JY, Baek KJ, Choi Y, Ji S. T helper 1 and 2 stimuli induce distinct phenotypes in gingival fibroblasts. Arch Oral Biol. 2019.
 
64. Hong J, Park HK, Park S, Lee A, Lee YH, Shin DY, Koh Y, Choi JY, Yoon SS, Choi Y, Kim I. Strong association between herpes simplex virus-1 and chemotherapy-induced oral mucositis in patients with hematologic malignancies. Korean J Int Med. In press.

 

Patents

1. Composition comprising Notoginseng Radix extract for preventing and treating of arthritis as an effective component. C-K Kim, Y Choi, D Chung, HJ Woo, SW Kim, HK Kim, SY Ko, JY Kim, SW Chang, DH Baeck, Korea Patent 10-0605114-0000,  US Patent 7595068 B2 (Sep. 29, 2009)

 

2. Iimmunosuppressive composition comprising Albizzia julibrissin Durazz extract as an effective component. Korea Patent 10-0605115-0000 C-K Kim, SW Kim, HK Kim, SY Ko, DH Baeck, SW Chang, BU Lee, Y Choi, JJ Kim

 

3. DNA probe for the detection of eubacteria. Y Choi, YC Kim Korea Patent 10-1497977 (Feb 25, 2015)

 

4. Method and kit for diagnosing Sjogren syndrome based on antigen-specific antibody detection.  J Alam, Y Choi. Korea Patent 10-1794403 Registered. 

 

5. Composition for treatment of recurrent aphthous stomatitis. HK Park, Y Kim, YS Choi, A Lee, Y Choi. Korea Patent 10-1734653 Registered.

6. 6. Y Choi. Epitope peptides specifically recognizing anti-aquaporin 5 autoantibodies and their use. Korea Patent 10- 1966515 registered.

7. Method of detecting or diagnosing Sjogren’s syndrome based on the presence of autoantibody against aquaporin 5 US patent Application No. 15/796,059 filed.