Development of the treatment by investigating the mechanism of disseminated BCG in patients with RORgT deficiency

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15528
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Hiroshima University
• Principal Investigator: Okada Satoshi 広島大学, 医歯薬保健学研究科(医), 講師 (80457241)
• Co-Investigator(Kenkyū-buntansha): 津村 弥来 広島大学, 医歯薬保健学研究科(医), 研究員 (80646274)
• Research Collaborator: ASANO TAKAKI 広島大学, 大学院医歯薬保健学研究科, 大学院生 ; HAYAKAWA SEIICHI 広島大学, 大学院医歯薬保健学研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: RORγT / RORC / MSMD / CMD / マイコバクテリア易感染症 / BCG / 慢性皮膚粘膜カンジダ症 / 原発性免疫不全症

Outline of Final Research Achievements

We performed whole exome analysis in patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) and/or Chronic Mucocutaneous Candidiasis (CMC). Through this study, we succeeded to identify two familial cases with RORγT deficiency. Two novel homozygous mutations in RORC, encoding RORγT, were identified. These two mutations introduced Jurkat cells, an immortalized line of human T lymphocyte cells, failed to upregulate IL17A mRNA, whereas WT RORC introduced cells upregulated them. We thus concluded that identified mutations were loss-of-function or severely hypomorphic. We are planning to pursue molecular mechanism of this disorder by investigating the patients’ cells, together with collecting detail clinical records.
Simultaneously, we have tried to generate inducible conditional-Rorc knockout mouse. We are now investigating generated mouse whether the genetic elimination is obtained by the pIpC injection.

Free Research Field

感染免疫学