Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis

Frontiers in Immunology

Asaf Wilensky¹  Oded Heyman¹  Thomas E. Van Dyke²  Gabriel Mizraji³ 

[1] Department of Periodontology, Faculty of Dental Medicine, Hebrew University of Jerusalem – Hadassah Medical Center, Jerusalem, Israel;Forsyth Institute, Cambridge, MA, United States;Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University of Jerusalem – Hadassah Medical Center, Jerusalem, Israel;

关键词: specialized pro-resolving lipid mediators;    resolvin;    periodontitis;    alveolar bone loss;    immune response;   

DOI  :  10.3389/fimmu.2018.00785

来源: DOAJ

【 摘 要 】

Periodontitis is an infectious inflammatory disease of the supporting structures of the teeth. Resolvins are part of a large family of specialized pro-resolving lipid mediators that enhance active resolution of inflammation and return of inflammatory lesions to homeostasis. In this paper, we demonstrate that resolvin D2 (RvD2), a product of docosahexaenoic acid (DHA) metabolism, prevents alveolar bone loss in Porphyromonas gingivalis-induced experimental periodontitis. Investigations of the immune mechanism of RvD2 actions reveal that 6 weeks after infection, the gingiva of RvD2-treated mice exhibit decreased CD4+ T-cells as well as lower RANKL expression levels and higher osteoprotegerin expression levels. Systemically, RvD2 prevents chronic secretion of IFN-γ and rapidly restores IFN-α levels, without dampening the P. gingivalis-specific immune response. In the gingiva, immediately after P. gingivalis inoculation, RvD2 regulates the mRNA expression of IFN-γ, IL-1β, TNF-α, and IL-10, hence contributing to maintaining local homeostasis. Moreover, RvD2 treatment reduces local neutrophil numbers, whereas pro-resolving macrophage counts were increased. These findings suggest that RvD2 resolves innate inflammatory responses, inhibiting systemic and gingival Th1-type adaptive responses that are known to mediate alveolar bone loss in this model.

【 授权许可】

Unknown