Elucidation of molecular mechanisms of maternal immune tolerance

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19430
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Miyazaki Masaki 京都大学, 医生物学研究所, 准教授 (80403632)
• Project Period (FY): 2022-06-30 – 2024-03-31
• 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

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.

Free Research Field

免疫学

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。