Interleukin (IL)-23 is an essential cytokine involved in expansion of the Th17 lineage, which is associated with many immune-related destructive tissue diseases. We hypothesized that the IL-23-induced Th17 pathway plays a role in periodontal pathology and examined the expression of cytokines, and related molecules, in periodontal lesions and control sites. IL-23 and IL-12 were expressed at significantly higher levels in periodontal lesions than in control sites. However, the relative expression of the IL-23 receptor compared with the IL-12 receptor β2 was significantly higher in periodontal lesions. Moreover, IL-17 expression was significantly higher in periodontal lesions, especially in the tissue adjacent to bone destruction, than in control sites. There was no significant difference in the expression levels of IFN-γ, an important cytokine inhibiting differentiation toward the Th17 pathway, between periodontal lesions and control sites. Together, these results suggest that the IL-23-induced Th17 pathway is stimulated in inflammatory periodontal lesions.
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References
1.
Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. -2007-. Phenotypic and functional features of human Th17 cells. J Exp Med204:1849–1861.
2.
Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, et al. -1999-. Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum42:963–970.
3.
Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al. -2007-. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature450:566–569.
4.
Ebersole JL, Taubman MA -1994-. The protective nature of host responses in periodontal diseases. Periodontol 20005:112–141.
5.
Gemmell E, Yamazaki K, Seymour GJ -2007-. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 200043:14–40.
6.
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. -2005-. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol6:1123–1132.
7.
Harrington LE, Mangan PR, Weaver CT -2006-. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol18:349–356.
8.
Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, et al. -2007-. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med204:41–47.
9.
Kirkham BW, Lassere MN, Edmonds JP, Juhasz KM, Bird PA, Lee CS, et al. -2006-. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study -the DAMAGE study cohort-. Arthritis Rheum54:1122–1131.
10.
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. -1999-. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest103:1345–1352.
11.
Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. -2005-. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med20:233–240.
12.
Nakae S, Saijo S, Horai R, Sudo K, Mori S, Iwakura Y -2003-. IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proc Natl Acad Sci USA100:5986–5990.
13.
Nakajima T, Ueki-Maruyama K, Oda T, Ohsawa Y, Ito H, Seymour GJ, et al. -2005-. Regulatory T-cells infiltrate periodontal disease tissues. J Dent Res84:639–643.
14.
Ohyama H, Ogata K, Takeuchi K, Namisato M, Fukutomi Y, Nishimura F, et al. -2005-. Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity. J Clin Pathol58:740–743.
15.
Ohyama H, Kato-Kogoe N, Nishimura F, Takeuchi-Hatanaka K, Matsushita S, Yamanegi K, et al. -2008-. Differential effects of polymorphisms in the 5′ flanking region of IL12RB2 on NK and T cell activity. J Interferon Cytokine Res28:563–569.
16.
Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. -2000-. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity13:715–725.
17.
Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. -2002-. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R. J Immunol168:5699–5708.
18.
Piskin G, Sylva-Steenland RM, Bos JD, Teunissen MB -2006-. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol176:1908–1915.
19.
Roberts FA, McCaffery KA, Michalek SM -1997-. Profile of cytokine mRNA expression in chronic adult periodontitis. J Dent Res76:1833–1839.
20.
Rogge L, Papi A, Presky DH, Biffi M, Minetti LJ, Miotto D, et al. -1999-. Antibodies to the IL-12 receptor β2 chain mark human Th1 but not Th2 cells in vitro and in vivo. J Immunol162:3926–3932.
21.
Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. -2006-. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med203: 2673–2682.
22.
Shaker OG, Moustafa W, Essmat S, Abdel-Halim M, El-Komy M. -2006-. The role of interleukin-12 in the pathogenesis of psoriasis. Clin Biochem39:119–125.
23.
Snyderman R, McCarty GA -1982-. Analogous mechanism of tissue destruction in rheumatoid arthritis and periodontal disease. In: Host-parasite interactions in periodontal diseases. Genco RJ, Mergenhagen SE, editors. Washington, DC: American Society for Microbiology, pp. 354–362.
24.
Steinman L -2007-. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell-mediated tissue damage. Nat Med13:139–145; erratum in Nat Med 13:385, 2007.
25.
Takahashi K, Azuma T, Motohira H, Kinane DF, Kitetsu S -2005-. The potential role of interleukin-17 in the immunopathology of periodontal disease. J Clin Periodontol32:369–374.
26.
Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, et al. -2000-. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature408:600–605.
27.
Takeichi O, Haber J, Kawai T, Smith DJ, Moro I, Taubman MA -2000-. Cytokine profiles of T-lymphocytes from gingival tissues with pathological pocketing. J Dent Res79:1548–1555.
28.
Takeuchi-Hatanaka K, Ohyama H, Nishimura F, Kato-Kogoe N, Soga Y, Matsushita S, et al. -2008-. Polymorphisms in the 5′ flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population. J Clin Periodontol35:317–323.
29.
Teng YT -2003-. The role of acquired immunity and periodontal disease progression. Crit Rev Oral Biol Med14:237–252.
30.
Tokoro Y, Matsuki Y, Yamamoto T, Suzuki T, Hara K -1997-. Relevance of local Th2-type cytokine mRNA expression in immunocompetent infiltrates in inflamed gingival tissue to periodontal diseases. Clin Exp Immunol107:166–174.
31.
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 Periodontol32:383–389.
32.
Yamazaki K, Nakajima T, Gemmell E, Polak B, Seymour GJ, Hara K -1994-. IL-4- and IL-6-producing cells in human periodontal disease tissue. J Oral Pathol Med23:347–353.
33.
Zaiss MM, Axmann R, Zwerina J, Polzer K, Gückel E, Skapenko A, et al. -2007-. Treg cells suppress osteoclast formation: a new link between the immune system and bone. Arthritis Rheum56:4104–4112.
