RANK/RANKL/OPG signaling upregulates IL-10 -regulated anti-inflammatory response during Candida albicans Infection

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Ohu University
• Principal Investigator: Kobayashi Michiyo 奥羽大学, 歯学部, 講師 (80316265)
• Co-Investigator(Kenkyū-buntansha): 坂本 直哉 北海道大学, 創成研究機構, 助教 (30466429) ; 奥村 一彦 北海道医療大学, 歯学部, 教授 (60194510)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Osteoprotegerin / RANKL / RANK / Candida albicans

Outline of Final Research Achievements

Receptor activator of nuclear factor-kappa B ligand (RANKL) to RANK interactions are critical to pathogenesis in immune cells. Osteoprotegerin (OPG) prevents binding of RANKL to RANK. This study utilized a mouse model (orally inoculated) to determine if there was a correlation between superficial candidiasis, commonly caused by the opportunistic fungus Candida albicans, and RANK/RANKL/OPG. Upregulation of OPG, RANKL, and RANK mRNA expression were found in mice whose oral cavity had a superficial C. albicans infection. Moreover, administration of exogenous soluble RANKL upregulated the mRNA of RANK in the infected tissue. Exogenous soluble RANKL also upregulated the mRNA of IL-10, which prompted anti-inflammatory effects including wound healing. Therefore, our data suggested that RANK/RANKL/OPG signaling might play a role in the pathogenesis of candidiasis, making this the first study to show the relationship between this opportunistic infection and the RANK/RANKL/OPG axis.

Free Research Field

口腔衛生学

Academic Significance and Societal Importance of the Research Achievements

カンジダ感染症は高齢者に発症率が高い内因性感染症である。高齢者は骨代謝因子Osteoprotegerin (OPG)の血清濃度が若年者、中年者に比較して高いことが報告されている。本研究結果はOPGやRANKLの局所の濃度がCandida albicans感染の発症、増悪に関与している可能性を示唆する。　これは内因性感染症であるC. albicansの発症を制御し、QOLを高かめて国民の健康寿命を延伸するうえで有益な結果であると考える。