| Project/Area Number |
22K19430
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
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| Keywords | リンパ球分化 / 免疫寛容 / B細胞分化 / 授乳期 / 遺伝子発現制御 / 妊娠・授乳期における免疫細胞分化 / T, B細胞分化 / 免疫反応 / T細胞分化 / 妊娠 / 授乳 / 胸腺 / 骨髄 / 免疫応答 |
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| Outline of Research at the Start |
妊娠中は非自己である胎児に対する拒絶反応が抑制されており、これを母体の免疫寛容と呼ぶ。妊娠・授乳期ではT細胞を産生する胸腺が萎縮し、骨髄のB細胞も減少し、ナイーブT、B細胞の供給が障害される。一方、妊婦でのワクチン反応は正常であり、単純な免疫抑制状態とは言えず、妊娠による免疫寛容の本態は明らかでない。本研究は、“妊娠・授乳期でのT, B細胞の分化や免疫応答の変動による免疫寛容の本態の解明とその分子機構を明らかにする”ことを目的とし、その為に妊娠・授乳期における免疫応答の変動を検証し、母体の免疫寛容の基盤を解明する。
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| Outline of Final Research Achievements |
During pregnancy, rejection of the non-self, the fetus, is suppressed, called maternal immune tolerance. During pregnancy and lactation, thymic atrophy and reduction of B cell development in bone marrow are suppressed, which impair the supply of naive T and B cells, however, the molecular mechanism is not clear. To elucidate the molecular mechanism of this defect, we first examined the bone marrow B cell development in weaning female mice produced by in vitro fertilization (IVF), in which several female mice were simultaneously impregnated. Interestingly, we found that pre-B cells were significantly reduced in lactating female mice. Therefore, pre-B cells were collected by sorting and analyzed for gene expression (RNA-seq). The GO analysis showed that the expression of several genes was upregulated in the inflammation- and infection-related genes rather than in the hormone-related genes. Further analysis will be conducted in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
妊娠期のリンパ球分化減少はよく知られているが、授乳期でのB細胞分化障害については殆ど知られていない。本研究により新たなリンパ球分化の抑制機構、そして免疫寛容の分子機構を解明し、将来的にはアレルギー反応の抑制や自己免疫疾患の新規治療へと繋げていきたい。そういう意味で、学術的だけでなく社会的にも意義の深い研究となることが期待される。
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