Effects of environmental chemicals on Th17 cells differenciation via aryl hydrocarbon receptor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene
• Research Institution: Hokkaido Institute of Public Health
• Principal Investigator: KOJIMA HIROYUKI 北海道立衛生研究所, 食品科学部, 主幹 (10414286)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Shinji 北海道立衛生研究所, 理化学部, 主査 (20414287) ; MUROMOTO Ryuta 北海道大学, 大学院薬学研究院, 助教 (30455597)
• Co-Investigator(Renkei-kenkyūsha): MATSUDA Tadashi 北海道大学, 大学院薬学研究院, 教授 (20212219)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 環境化学物質 / AhR / IL17 / Th17 / ROR / 自己免疫疾患 / ダイオキシン / レポーターアッセイ

Outline of Final Research Achievements

The retinoic acid receptor-related orphan receptor (ROR) and aryl hydrocarbon receptor (AhR) are key regulators of helper T (Th)17 cell differentiation. However, it remains unclear whether environmental chemicals, including dioxins, affect Th17 cell functions. In this study, we examined the AhR activity of 200 environmental chemicals using DR-EcoScreen assay, and found that several pesticides and isoflavones enhanced AhR-mediated transcriptional activity. These compounds increased the expression of IL-17A mRNA without effecting ROR mRNA levels in mouse T lymphoma EL4 cells. On the other hand, these chemicals did not affect the IL-17A gene expression in ROR- or AhR-knockdown EL4 cells. Taken together, these results suggest that several AhR agonists might enhance IL-17 production via ROR and AhR. This study also provides the evidence that environmental chemicals can act as modulators of IL-17 gene expression in immune cells.

Free Research Field

衛生学、環境毒性学、免疫学