Mechanisms and consequences of elimination of unwanted cells by programmed phagocytosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04762
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kanazawa University
• Principal Investigator: Nakanishi Yoshinobu 金沢大学, 薬学系, 特任教授 (40172358)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 感染症 / 癌 / シグナル伝達 / 免疫学 / 薬学

Outline of Final Research Achievements

Unwanted own cells that emerge in multicellular organisms undergo structural changes, through apoptosis for example, and are eliminated by phagocytosis. This phenomenon contributes to the maintenance of tissue homeostasis. We named this phenomenon as ‘Programmed Phagocytosis’ and intended to clarify its mechanisms and consequences using Drosophila melanogaster as an animal model.
We first showed the existence of two signaling pathways for the induction of phagocytosis of apoptotic cells. Then, we found that phagocytes increase their phagocytic activity through enhanced expression of engulfment receptors upon the engulfment of apoptotic cells, and interpreted this event as 'Phagocyte Priming' to ensure the elimination of unwanted cells that phagocytes encounter thereafter. Finally, we showed that programmed phagocytosis lessens the pathology of viral diseases and cancer.

Free Research Field

免疫生化学

Academic Significance and Societal Importance of the Research Achievements

学術的意義：本研究の成果は、プログラム細胞貪食が不要自己細胞の安全な排除のための主要な反応であり、その仕組みは種を越えて保存されていることを示した。そして、自然免疫が生体を外的の侵入から守る役割だけでなく、生体内で生じた変性細胞を排除することで恒常性維持にも寄与することが明らかになった。
社会的意義：原因が不明とされる疾患の中に、プログラム細胞貪食の不全によって発症するものが見つかる可能性がある。また、プログラム細胞貪食を亢進させて疾患の予防や治療を行う医療の開発も期待される。