Studies on thyroid autoimmunity: anti-TSHR immune response and tolerance in mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: NAGAYAMA Yuji 長崎大学, 原爆後障害医療研究所, 教授 (30274632)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: バセドウ病 / マウスモデル / TSH受容体

Outline of Final Research Achievements

We have recently shown that (i) wt mice are tolerant, while TSHR KO mice are responsive to the mouse receptor in a mouse model of Graves’ disease using adenovirus expressing mouse TSHR, and (ii) anti-TSHR immune response could be adoptively transferred from TSHR KO to nude mice but that hyperthyroidism and TSAb were transient and soon changed to hypothyroidism and TBAb. Therefore, we here studied (i) the mechanisms of immune tolerance and response in wt KO mice, respectively, and (ii) those of immune response in the adoptive transfer model. In the evaluation of the peripheral tolerance, inhibition of co-inhibitory molecules and stimulation of co-stimulatory molecules increased the anti-TSHR antibodies, but did not develop TSAb or hyperthyroidism. On the other hand, the studies on central tolerance did not technically work well. In the adoptive transfer model, Graves’ disease could be maintained by repetitive immunization following transfer.

Free Research Field

内分泌学