The Role of transcription factor Eos in dendritic cells development in gut immunity

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K07956
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: Ohoka Yoshiharu 徳島文理大学, 薬学部, 教授 (60303971)
• Research Collaborator: Nakatsuma Aya (Yokota Aya)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 樹状細胞 / レチノイン酸 / RALDH2 / Eos / 転写因子 / Ikarosファミリー / 免疫寛容

Outline of Final Research Achievements

Retinal dehydrogenase 2 (RALDH2) encoded by Aldh1a2 plays key roles in generating RA in dendritic cells (DCs) in gut-related lymphoid organs. To identify gene involved in the regulation of Aldh1a2 gene expression, gene expression of GM-CSF/LPS-treated and untreated BM-DCs was measured using DNA microarray. We identified Eos (ikzf4) gene whose expression was up-regulated by GM-CSF/LPS treatment in BM-DCs. Eos is a member of a zinc-finger transcription factor of the Ikaros (ikzf1) family. Eos siRNA partially downregulated Aldh1a2 gene in GM-CSF/LPS-treated BM-DCs. The expression of Eos mRNA was observed in MLN-DC but not in SPL or PLN in a manner similar to Aldh1a2 mRNA. Furthermore, both Eos and RALDH2 mRNA is specifically expressed in MLN-DC subset, CD11b±CD8α-CD103+ which has been thought to be a retinoic acid-producing anti-inflammatory DCs. These results suggest that Eos may be involved in the regulation of Aldh1a2 gene expression in DCs in gut-related lymphoid organs.

Free Research Field

免疫学　分子生物学　生化学

Academic Significance and Societal Importance of the Research Achievements

腸管免疫系においては免疫反応の促進と抑制のバランスを保つことが重要であり、その乱れは様々なアレルギー疾患や炎症性腸疾患発症等を引き起こす。この腸管免疫系における免疫反応のバランスの制御には、ビタミンAの代謝物であるレチノイン酸が重要な役割を果たしており、その産生酵素RALDH2の発現制御機構に転写因子Ikarosファミリーに属するEos遺伝子が関与することが明らかになった。この成果は今後、アレルギー疾患や炎症性腸疾患発症等の治療を目的とした新たな創薬ターゲットの分子基盤構築に貢献することが期待される。