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Koike, E.

Publications and source records attributed to Koike, E..

2 recordsLinked to original sources
bioRxiv2025

IL-18 produced by pregnant uterus promotes essential inflammatory responses and fetoplacental growth

Placental insufficiency affects fetomaternal health throughout life. Although the interaction between the maternal uterine immune milieu and fetal-derived cells plays a crucial role in placental formation, several aspects remain unclear. Therefore, we conducted this study to investigate the effects of interleukin (IL)- 18, a unique cytokine with both proinflammatory and anti-inflammatory properties, on the uterine immune milieu and placental development. Our results identified pregnant uterine smooth muscle cells as an important source of IL-18, which supports homeostatic type 1 immune responses. IL-18 facilitates appropriate placental development through uterine vascular remodeling and placental angiogenesis. Smooth muscle cell-specific Il18-knockout dam mice exhibited impaired fetoplacental growth and elevated maternal blood pressure, reflecting preeclampsia-like phenotypes. Their offspring demonstrated a tendency toward excessive weight gain and delayed neurodevelopment. Overall, this study emphasizes the essential role of IL-18 in placental formation and its wider implications for fetomaternal health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/649615v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@27862eorg.highwire.dtl.DTLVardef@da4786org.highwire.dtl.DTLVardef@8dd7e2org.highwire.dtl.DTLVardef@584c41_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISmooth muscle cells in the pregnant uterine myometrium sufficiently produce IL-18 C_LIO_LIIL-18 induces type 1 immune responses in the uterine immune milieu C_LIO_LIIL-18 promotes maternal uterine vascular remodeling and placental angiogenesis C_LIO_LIIL-18-signaling deficiency in the mouse model shows the preeclampsia-like clinical course C_LI

immunology↗
bioRxiv2019

A novel effect of the antigenic peptides position for presentation upon MHC class I

MHC-I molecules are expressed on the cell surface complexed with oligopeptides, most of which are generated from intracellular proteins by the ubiquitin-proteasome pathways and would be roughly proportional to the relative abundance of proteins and their rate of degradation. Thus MHC-I together with peptides function as immunological self-markers to exhibit the information about the repertoire of proteins expressed in a given cell to the immune system, and this process is called antigen (Ag) direct-presentation. Herein, we report a novel rule for the preference of peptides selected for the direct presentation; the N-terminally located antigenic peptides are more efficiently complexed with MHC-I than the C-terminally located peptides on the same protein. The superiority is largely dependent upon de novo proteins synthesis, degradation by proteasomes, and less dependent upon stabilities of proteins, indicating that this difference derived from rapidly degraded newly synthesized proteins such as defective ribosomal products (DRiPs). The effects of those N-terminal predominance was comparable with the enhanced MHC-I presentation by IFN-{gamma} suggesting that they might play important roles in the adaptive immunity.

immunology↗