Comprehensive analysis of innate immunity

2019 Fiscal Year Final Research Report

• Project/Area Number: 15H05704
• Research Category: Grant-in-Aid for Specially Promoted Research
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: AKIRA Shizuo 大阪大学, 免疫学フロンティア研究センター, 特任教授 (50192919)
• Co-Investigator(Kenkyū-buntansha): SATOH Takashi 大阪大学, 免疫学フロンティア研究センター, 准教授 (60619716) ; KUNIYOSHI Kanako 大阪大学, 微生物病研究所, 特任研究員 (70747881) ; MAEDA Kazuhiko 大阪大学, 免疫学フロンティア研究センター, 特任准教授 (20332869) ; TANAKA Hiroki 大阪大学, 免疫学フロンティア研究センター, 特任助教 (50747920)
• Project Period (FY): 2015 – 2019
• Keywords: 自然免疫 / mRNA安定性制御 / M2マクロファージ / 炎症

Outline of Final Research Achievements

We try to understand the biological and mechanical features in innate immunity using the knockout mice model. We focused on two new research fields: “mRNA stability mechanism” and “disease-specific macrophage subset”. We have showed that phosphorylation of endonuclease Regnase-1 upon inflammatory stimuli is essential for the mRNA stabilization of several inflammation-associated genes. We have also found that Regnase-1 controls colon epithelial regeneration through the mRNA degradation of genes associated with mTOR signaling pathway and purine metabolism. We discovered the new macrophage subset, named SatM, which were critical for the development of fibrosis. Differentiation of SatM cells was governed by CEBP/β expression and these cells were derived from the different progenitor of conventional macrophage lineage. This finding may be possible to develop novel, more specific therapeutic targets with fewer side effects. In addition, we found that the interferon-induced transcription factor Batf2 has an antitumor effect through the TLR7-induced IL-12 production in tumor-associated macrophages, implicating that Batf2 may be an important target in antitumor treatment.

Academic Significance and Societal Importance of the Research Achievements

疾患の発症及び増悪メカニズムの関係性の解明を目指し、代表者らが開拓した自然免疫における新しい二つの分野において独創的観点から研究に取り組み、炎症、線維症、癌に関わる重要な免疫作用を発見した。これらの成果は、様々な免疫関連疾患の原因、治療と克服に向けた新領域・創薬研究の推進を促すことが期待できる。

Free Research Field

医歯薬学
免疫学