Studies aiming the establishing self-tolerance for the cure of autoimmune disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293223
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUMOTO Mitsuru 徳島大学, 疾患酵素学研究センター, 教授 (60221595)
• Co-Investigator(Kenkyū-buntansha): NISHIJIMA Hitoshi 徳島大学, 疾患酵素学研究センター, 助教 (60425410) ; MOURI Yasuhiro 徳島大学, 疾患酵素学研究センター, 助教 (80464353)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: AIRE / thymus / autoimmunity

Outline of Final Research Achievements

Cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs) play essential roles in the positive and negative selection, respectively. Aire in mTECs plays an essential role in the latter. We used BAC technology to establish a semiknockin strain expressing Aire under control of the promoter of β5t, a thymoproteasome expressed exclusively in the cortex. Although Aire was expressed in cTECs as typical nuclear dot protein, cTECs expressing Aire ectopically did not confer transcriptional expression of Aire-dependent tissue-restricted antigen genes. We also established a novel Aire reporter strain in which endogenous Aire is replaced by the human AIRE-GFP-Flag tag gene. The hAGF reporter protein was produced and retained very efficiently within mTECs as authentic Aire nuclear dot protein. Remarkably, snapshot analysis revealed that mTECs expressing hAGF accounted for >95% of mature mTECs, suggesting that Aire expression does not represent a particular mTEC lineage(s).

Free Research Field

免疫学