Molecular mechanism of thymic involution and its application to forensic diagnosis of child abuse

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H03067
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 58040:Forensics medicine-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Kondo Toshikazu 和歌山県立医科大学, 医学部, 教授 (70251923)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 法医病理学 / 子どもの虐待 / 胸腺退縮 / サイトカイン / ケモカイン / アポトーシス / 副腎皮質ホルモン

Outline of Final Research Achievements

We analyzed the roles of cytokines/chemokines in thymic atrophy using murine restraint stress model. When WT mice were restrained, the thymus was significantly involuted. However,in Cx3cr1-deficient mice treated with the same manner, the thymic atrophy was significantly suppressed. Subsequently, we examined apoptotic cells in the thymus of WT and Cx3cr1-deficient mice. Restrain stress induced the apoptosis in the thymic cells of WT mice. However,the absence of Cx3cr1 significantly suppressed apoptosis of thymic cells. In line with this,the intrathymic gene expression of Fas ligand was significantly attenuated in Cx3cr1 deficient mice．Moreover, blood cortisol level was suppressed in restrain stress-treated Cx3cr1-deficient mice. These observations implied that the absence of CX3CR1 resisted stress-induced thymic atrophy. Thus, CX3CR1-mdiated signals would promote thymic involution induced by restrain stress. CX3CR1 would be a key molecule for diagnosing abuse in infants and children.

Free Research Field

法医学

Academic Significance and Societal Importance of the Research Achievements

法医解剖例・臨床医学の現場において，虐待が疑われる事例については医学的見解を求められることが多くなってきている．そこで被虐待児の鑑別法の確立が切望されているにも関わらず被虐待児であると判断するための客観的な法医学的診断法は未だ確立されていない．CX3CR1遺伝子欠損マウスではストレスによる胸腺退縮が有意に抑制されていことから，CX3CR1がストレス誘導胸腺退縮に重要な役割を果たしていることが世界で初めて明らかとなった．法医学的に血中のCX3CL1（CX3CR1リガンド）CX3CR1が，虐待のバイオマーカーの一つとなる可能性が示され，今後の新たな虐待の法医診断法の確立に貢献するものと考えられた．