Th17 Cells in Gingival Immunity and Their Key Role in Periodontitis Pathogenesis Item Type dissertation Authors Dutzan, Nicolas Publication Date 2017 Abstract Periodontitis is a very common human disease characterized by inflammatory bone destruction in the oral cavity. It affects more than 64 million adults in the United States and is often linked to systemic or distant co-morbidities. T helper (Th) cell... Keywords bone loss; IL-17; STAT3; Interleukin-17; Periodontitis; Th17 Cells Download date 27/09/2021 19:02:00 Link to Item http://hdl.handle.net/10713/7340 Curriculum Vitae Name: Nicolas Raul Dutzan Munoz E-mail: [email protected] Education: 2003 DDS, University of Chile, Chile 2008 MSc in Periodontology, University of Chile, Chile 2011 Certificate in Periodontics, University of Chile, Chile 2017 PhD, Oral and Experimental Pathology, Graduate School, University of Maryland Baltimore/National Institutes of Health Brief Chronology of Employment: 2003-2013 Private Dental Practice, Santiago, Chile. 2003-2013 Research Fellow, Periodontal Biology Laboratory, Conservative Dentistry Department, Faculty of Dentistry, University of Chile, Chile. 2007-Today Assistant Professor, Conservative Dentistry Department, Faculty of Dentistry, University of Chile, Chile. 2013-Today Visiting Fellow, National Institute of Dental and Craniofacial Research, National Institutes of Health. Professional Society Membership: International Association for Dental Research Sociedad Chilena de Periodoncia American Association of Immunologists Society for Mucosal Immunology Asociación Chilena de Inmunología Academic Honors and Awards: 2005 International Association for Dental Research, Division Chile, Distinguished Annual Research Award. 2005 Dentistry Faculty Scholarship for the MSc in Periodontology, University of Chile. 2005 Dentistry Faculty Scholarship for the Periodontics Residency, University of Chile. 2011 Best Resident Award. Faculty of Dentistry, University of Chile 2013 Chilean National Scholarship Program for Graduate Studies 2017 Fellows Award for Research Excellence (FARE) 2018, National Institutes of Health Editorial Responsibilities-Ad Hoc Reviewer: 2015-Present Oral Diseases 2016-Present Archives of Oral Biology 2016-Present Journal of Periodontal Research IRB Approved Clinical Protocols: Associate Investigator: 12-D0100(NCT01568697): Oral Microbial and Immunological Characterization of Patients with Immune Dysfunction (Recruiting) Peer Reviewed Research Articles: 1. Vernal R, Dutzan N, Chaparro A, Puente J, Antonieta Valenzuela M, Gamonal J. 2005. Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. J Clin Periodontol 32: 383-389. 2. Vernal R, Dezerega A, Dutzan N, Chaparro A, León R, Chandía S, Silva A, Gamonal J. 2006. RANKL in human periapical granuloma: possible involvement in periapical bone destruction. Oral Dis 12:283-289. 3. Vernal R, Dutzan N, Hernandez M, Chandía S, Puente J, León R, García L, Del Valle I, Silva A, Gamonal J. 2006. High expression levels of receptor activator of nuclear factor-kappa B ligand associated with human chronic periodontitis are mainly secreted by CD4+ T lymphocytes. J Periodontol 77:1772-1780. 4. Silva N, Dutzan N, Hernandez M, Dezerega A, Rivera O, Aguillon JC, Aravena O, Lastres P, Pozo P, Vernal R, Gamonal J. 2008. Characterization of progressive periodontal lesions in chronic periodontitis patients: levels of chemokines, cytokines, matrix metalloproteinase-13, periodontal pathogens and inflammatory cells. J Clin Periodontol 35:206-214. 5. Dutzan N, Vernal R, Hernandez M, Dezerega A, Rivera O, Silva N, Aguillon JC, Puente J, Pozo P, Gamonal J. 2009. Levels of interferon-gamma and transcription factor T-bet in progressive periodontal lesions in patients with chronic periodontitis. J Periodontol 80:290-296. 6. Dutzan N, Gamonal J, Silva A, Sanz M, Vernal R. 2009. Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL) -17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis. J Clin Periodontol 36:396-403. 7. Hernandez Rios M, Sorsa T, Obregon F, Dutzan N, Lesaffre E, Molas M, Gamonal J. 2009. Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade. J Clin Periodontol 36:1011-1017. 8. Dezerega A, Pozo P, Hernandez M, Dutzan N, Gutiérrez-Fernández A, Overall CM, Garrido M, Alcota M, Ortiz E, Gamonal J. 2010. Chemokine monocyte chemoattractant protein-3 in progressive periodontal lesions in patients with chronic periodontitis. J Periodontol 81:267-276. 9. Dezerega A, Osorio C, Mardones J, Mundi V, Dutzan N, Franco M, Gamonal J, Oyarzún A, Overall CM, Hernández M. 2010. Monocyte chemotactic protein-3: possible involvement in apical periodontitis chemotaxis. Int Endod J 43(10):902- 10. Hernández M, Gamonal J, Tervahartiala T, Mäntylä P, Rivera O, Dezerega A, Dutzan N, Sorsa T. 2010. Associations between matrix metalloproteinase-8 and - 14 and myeloperoxidase in gingival crevicular fluid from subjects with progressive chronic periodontitis: a longitudinal study. J Periodontol. 81(11):1644-52. 11. Dutzan N, Vernal R, Vaque JP, García-Sesnich J, Hernandez M, Abusleme L, Dezerega A, Gutkind JS, Gamonal J. 2012. Interleukin-21 expression and its association with proinflammatory cytokines in untreated chronic periodontitis patients. J Periodontol. 83(7):948-54 12. Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, Gamonal J, Diaz PI. 2013. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J. 7(5):1016-25 13. Navarrete M, García J, Dutzan N, Henríquez L, Puente J, Carvajal P, Hernandez M, Gamonal J. 2014. Interferon-γ, interleukins-6 and -4, and factor XIII-A as indirect markers of the classical and alternative macrophage activation pathways in chronic periodontitis. J Periodontol. 85(5):751-60. 14. N. M. Moutsopoulos, J. Konkel, M. Sarmadi, M. A. Eskan, T. Wild, N. Dutzan, L. Abusleme, C. Zenobia, K. B. Hosur, T. Abe, G. Uzel, W. Chen, T. Chavakis, S. M. Holland, G. Hajishengallis 2014.Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17–driven inflammatory bone loss. Sci. Transl. Med. 6, 229ra40 15. González FE, Ortiz C, Reyes M, Dutzan N, Patel V, Pereda C, Gleisner MA, López MN, Gutkind JS, Salazar-Onfray F. 2014. Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells. Immunology.142(3):396-405 16. Moutsopoulos NM, Chalmers NI, Barb JJ, Abusleme L, Greenwell-Wild T, Dutzan N, Paster BJ, MunsonPJ, Fine DH, Uzel G, Holland SM. 2015. Subgingival microbial communities in Leukocyte Adhesion Deficiency and their relationship with local immunopathology. PLoS Pathog. 5;11(3) 17. Díaz L, Hoare A, Soto C, Bugueño I, Silva N, Dutzan N, Venegas D, Salinas D, Pérez-Donoso JM, Gamonal J, Bravo D. 2015. Changes in lipopolysaccharide profile of Porphyromonas gingivalis clinical isolates correlate with changes in colony morphology and polymyxin B resistance. Anaerobe. 33:25-32 18. Dutzan N, Abusleme L, Konkel JE, Moutsopoulos NM. 2016. Isolation, characterization and functional examination of the gingival immune cell network. Journal of Visualized Experiments. 16;(108) 19. Dutzan N, Konkel JE, Wild T, Moutsopoulos NM. 2016. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunology. 2016 Sep;9(5):1163-72. 20. Dutzan N, Abusleme L, Bridgeman H, Greenwell-Wild T, Zangerle-Murray T, Fife ME, Bouladoux N, Linley H, Brenchley L, Wemyss K, Calderon G, Hong BY, Break TJ, Bowdish DM, Lionakis MS, Jones SA, Trinchieri G, Diaz PI, Belkaid Y, Konkel JE, Moutsopoulos NM. On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity. 2017 Jan 17;46(1):133-147. 21. Moutsopoulos, N.M., Zerbe, C.S., Wild, T., Dutzan, N., Brenchley, L., Uzel, G., Chandler, K.C., Lisco, A., Hajishengallis, G., Notarangelo, L., Holland, SM. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type. N Engl J Med. 2017 Mar 23;376(12):1141-1146. Peer Reviewed Review Articles: 1. Hernández M, Dutzan N, García-Sesnich J, Abusleme L, Dezerega A, Silva N, González FE, Vernal R, Sorsa T, Gamonal J. 2011. Host-pathogen interactions in progressive chronic periodontitis. J Dent Res. 90(10):1164-70. 2. Silva N, Abusleme L, Bravo D, Dutzan N, Garcia-Sesnich J, Vernal R, Hernández M, Gamonal J. 2015. Host response mechanisms in periodontal diseases. J Appl Oral Sci. 23(3):329-55. Title of Dissertation: Th17 Cells in Gingival Immunity and Their Key Role in Periodontitis Pathogenesis Nicolas Dutzan, DDS, Doctor of Philosophy, 2017 Dissertation directed by: Niki M. Moutsopoulos, DDS, PhD, Tenure Track Clinical Investigator, Oral Immunity and Infection Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health Abstract: Periodontitis is a very common human disease characterized by inflammatory bone destruction in the oral cavity. It affects more than 64 million adults in the United States and is often linked to systemic or distant co-morbidities. T helper (Th) cells and specifically Th17 have been identified as important constituents of the inflammatory lesion in periodontitis. However, the specific role of Th17 cells