Analysis of molecular mechanism of granuloma formation by autoinflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08784
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kyoto University (2020-2021); Kansai Medical University (2019)
• Principal Investigator: Kambe Naotomo 京都大学, 医学研究科, 准教授 (50335254)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肉芽腫 / iPS細胞 / ブラウ症候群

Outline of Final Research Achievements

The mechanism of granuloma formation remains unclear, and no specific treatment has been established. We have studied Blau syndrome, a single gene disease, as a model for granuloma formation. Blau syndrome is a disease in which a gain-of-function mutation in the NOD2 gene causes granuloma formation in the skin, joints, and eyes through an autoinflammatory mechanism. We have reported the results of our original method, including the establishment of patient-derived iPS cells. However, comprehensive analysis of gene and protein expression did not reveal any differences between Blau syndrome and healthy controls, and no clue to the pathological analysis of granuloma formation, which characterizes Blau syndrome, has been found. In contrast, the analysis focusing on phosphorylation, a post-translational modification, has allowed us to identify the immunoregulatory mechanism of Molecule A, which is currently being analyzed.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

肉芽腫形成のメカニズムには不明な点が多く，特異的治療法も確立していない。皮膚・関節・眼に肉芽腫を形成する単一遺伝子病であるブラウ症候群は，国内での報告例が50例程度の希少疾患であるが，NOD2遺伝子の機能獲得型変異により自己炎症的機序から肉芽腫を形成する疾患であることから，肉芽腫形成のメカニズムを解明する上でのモデルとして適している。本研究において，タンパク翻訳後修飾の１つであるリン酸化に着目した解析から，分子Aを同定した。この分子A自身も翻訳後修飾に関わる分子であり，肉芽腫形成のメカニズムに翻訳後修飾が関わっている可能性という新たな病態解明の糸口が見出された。