Laeverin/aminopeptidase Q induces indoleamine 2,3-dioxygenase-1 in human monocytes

Takuma Suzuki; Takashi Iizuka; Kyosuke Kagami; Takeo Matsumoto; Rena Yamazaki; Takiko Daikoku; Akihito Horie; Masanori Ono; Akira Hattori; Hiroshi Fujiwara

doi:10.1016/j.isci.2023.107692

Laeverin/aminopeptidase Q induces indoleamine 2,3-dioxygenase-1 in human monocytes

iScience. 2023 Aug 19;26(9):107692. doi: 10.1016/j.isci.2023.107692. eCollection 2023 Sep 15.

Authors

Affiliations

¹ Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
² Division of Animal Disease Model, Research Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, Japan.
³ Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁴ Department of Obstetrics and Gynecology, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan.
⁵ Department of System Chemotherapy and Molecular Sciences, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan.

Abstract

Human extravillous trophoblast (EVT) invades the maternal endometrium and reconstructs uterine spiral arteries cooperatively with maternal immune cells. Although EVT has allogeneic paternal antigens, the maternal immune system does not reject it. Here, we found that laeverin (LVRN), an EVT-specific cell surface peptidase, interacts with monocytes to produce indoleamine 2,3-dioxygenase-1 (IDO1). LVRN-transfected Swan71 cells, a cytotrophoblast-derived cell line, and increased IDO1 expression in PBMC under cell-to-cell interacting conditions. Soluble recombinant LVRN (r-LVRN) interacted with CD14-positive monocytes and induced their IDO1 expression without the intervention of other immune cell populations. LVRN-induced IDO1 production was promoted in PMA-activated monocyte-like THP-1 cells. Furthermore, r-LVRN decreased the tryptophan level and increased the kynurenine/tryptophan ratio in the culture media of the PMA-treated THP-1 cells. These findings suggest that LVRN is one of the key molecules that mediate the interaction between EVT and monocytes/macrophages and creates an immunosuppressive environment at the maternal-fetal interface in the uterus.

Keywords: Developmental biology; Embryology; Molecular biology.