The study of the mechanism of maternal-fetal immune tolerance in dogs focusing on MDSC

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K14989
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: Kobayashi Masato 日本獣医生命科学大学, 獣医学部, 講師 (60898063)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胎子免疫寛容 / リラキシン / MDSC / 妊娠 / 犬

Outline of Final Research Achievements

MDSC suppress immune activity and maintain immune tolerance. However, the role of MDSC in maternal-fetal immune tolerance remains unclear. Herein, we investigated MDSC in the blood of pregnant canines and its induction mechanism. By analyzing MDSC in the blood of pregnant canines, elevation of MDSC which inhibit T cell activation has been observed. These results suggest that the elevated MDSC in canine pregnancy may contribute to reduces maternal immune activity. To clarify the cause of MDSC elevation in canine pregnancy, we analyzed the relationship between pregnancy-related hormones and MDSCs. Serum relaxin levels were correlated with the ratio of monocyte MDSC. Additionally, relaxin induced monocytic MDSC as well as inhibited T cell activation. Thus, relaxin contributes to the elevation of monocytic MDSC in the blood of pregnant canines. Our findings highlight the novel role of relaxin in pregnancy and contribute to a better understanding of maternal-fetal immune tolerance.

Free Research Field

獣医学

Academic Significance and Societal Importance of the Research Achievements

本研究より、リラキシンのMDSC誘導能による免疫抑制作用を明らかにした。リラキシンは妊娠期間中のみ分泌されるホルモンのため、妊娠犬の母体免疫抑制にリラキシンが関与していると考えられる。胎子に対する母体免疫抑制（胎子免疫寛容）は正常な妊娠を行うために必要な機構であるが、この胎子免疫寛容が正常に誘導されない場合、着床不全や早期流産を引き起こすと考えられている。本研究により明らかになったリラキシンの免疫抑制機構は今後の胎子免疫寛容機構解明に重要な知見であり、不妊治療に貢献すると考えられる。