A new inflammatory cytokine on the block: Re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17

For almost two decades, the Th1/Th2 paradigm has offered a productive conceptual framework for investigating the pathogenesis of periodontitis. However, as with many other inflammatory diseases, the observed role of T-cell-mediated immunity in periodontitis did not readily fit this model. A new subset of CD4+ T-cells was recently discovered that explains many of the discrepancies in the classic Th1/Th2 model, and has been termed Th17 based on its secretion of the novel proinflammatory cytokine IL-17. The identification of Th17 cells as a novel effector T-cell population compels re-examination of periodontitis in the context of the new subset and its signature cytokines. This review aims to offer a clarifying insight into periodontal pathogenesis under the extended Th1/Th2/Th17 paradigm, and is predicated on the principle that periodontal disease activity is determined by a complex interplay between the immune system and periodontal pathogens. The re-examination of existing periodontal literature and further studies in the light of these new discoveries may help explain how the inflammatory response results in damage to the periodontium while generally failing to control the pathogens. This knowledge is essential for the development of immunomodulatory intervention strategies for fine-tuning the host response to maximize the protective and minimize the destructive aspects of the periodontal host response. Moreover, with the advent of anti-cytokine biologic drugs that target the Th1 and Th17 pathways in autoimmunity, the potential consequences to periodontal disease susceptibility in humans need to be understood. Abbreviations: CIA, collagen-induced arthritis; CMI, cell-mediated immunity; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; ERK, extracellular signal-regulated kinase; IL-, interleukin; IRF, interferon regulatory factor; KO, knockout; PGE2, prostaglandin E2; PRR, pattern-recognition receptor; ROR, retinoic acid receptor; TCR, T-cell receptor; Th, T helper; TLR, Toll-like receptor; TRIF, TIR-domain-containing adapter protein-inducing interferon-beta.