The altered immune response caused by CCDC22 mutation and its association with EBV-HLH development and severity.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17405
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Yamashita Yusuke 和歌山県立医科大学, 医学部, 助教 (50794153)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CCDC22 / EBV-HLH / NFκB

Outline of Final Research Achievements

We conducted a functional analysis of the CCDC22V38M mutation, which was identified in a patient with severe EBV-HLH. NFκB activity was unaffected by forced expression of CCDC22 in HEK293T cells. However, the V38M mutation altered its intracellular localization. Knockdown of CCDC22 in Neuro2a cells resulted in impaired neuronal differentiation. CCDC22V38M mice did not significantly differ from wild type in their natural course. RNAseq of MEFs revealed alterations in the expressions of cytokine- and chemokine-related gene. Although this study does not establish a direct link between the CCDC22V38M mutation and the development of HLH, it suggests that CCDC22 plays an important role in the functioning of the nervous and immune systems.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、難治性疾患であるEBV-HLHの重症例より同定したCCDC22新規遺伝子変異の解析を行った。本研究ではCCDC22の免疫系への関与が示唆される新知見が得られた。CCDC22については、NFκBの調節因子であることや、タンパクの細胞内輸送に関わることなど報告されているものの、まだ機能は十分に解明されていない。本研究成果を足がかりにCCDC22の機能解析が進めば、免疫系の新たな調節機構の解明や、EBV-HLHの病態解明に貢献できる可能性がある。