What is the role of regulatory T cell via estrogen receptor in pregnacy maintenance and glucose metabolism.

Research Project

Project/Area Number	17K16838
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Obstetrics and gynecology
Research Institution	University of Toyama
Principal Investigator	Sameshima Azusa 富山大学, 附属病院, 助教 (80778465)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	エストロゲン / 更年期 / 糖尿病 / 妊娠糖尿病 / 不育症 / 制御性T細胞 / 糖代謝 / 妊娠
Outline of Final Research Achievements	Estrogen is one of the most important hormones, regulating sexual function and reproduction. Estrogen is also known to be multi-functional, with roles in the regulation of glucose metabolism, the maintenance of bone turnover, and immunological mechanism especially in women. We aimed to clarify the impact of estrogen receptor alpha deletion in T cells on the glucose metabolism, T cell distribution, and chronic inflammation in obese and gestational diabetes mellitus mice model. Estrogen receptor alpha of T cells contributes to the maintenance of glucose metabolism in gestational diabetes mellitus condition with high E2 environment, possibly by controlling localization of regulatory T cells and helper T cells. Female ovariectomized mice showed glucose intolerance after 4 weeks on the high fat diet. Expression levels of some genes were fluctuated in perigonadal adipose tissue after 1 week. These genes may prevent the development of diabetes in postmenopausal women.
Academic Significance and Societal Importance of the Research Achievements	本研究はエストロゲンの免疫、特に制御性T細胞を介した代謝制御の研究であり、独創性が高い。妊娠期の母児免疫寛容に重要であるTregの増加の機序にエストロゲン受容体は必須ではないことが初めて明らかになった。女性は閉経後、早期に肥満、糖尿病を発症するのではなく、5-10年のタイムラグがあり、この期間は未病状態にあると考えられる。この時期に介入することで閉経後の肥満、糖脂質代謝異常を予防できる可能性がある。本研究による未病状態の脂肪組織の変化は予防医学的観点からも意義深いと考えられる。