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The Fetal-Maternal Immune Interface in Uterus Transplantation.

ABSTRACT: Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a unique clinical and experimental model. We posit that understanding the distinct immunological properties at the interface of the transplanted uterus, the fetus and maternal circulation might provide valuable novel insights while improving outcomes for UTx. Here, we discuss immunological challenges and opportunities of UTx affecting mother, pregnancy and healthy livebirths.

SUBMITTER: Iske J

PROVIDER: S-EPMC7879580 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Fetal-Maternal Immune Interface in Uterus Transplantation.

Iske Jasper J Elkhal Abdallah A Tullius Stefan G SG

Trends in immunology 20200301 3

Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a uniq ...[more]

PMID: 32109373

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Project description:ContextDysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive.ObjectiveTo determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion.DesignFirst trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo.ResultsCBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual T-helper 1/T-helper 2 imbalance in mice, which was partially rescued by H2S donors.ConclusionCBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.

Dataset Information

The Fetal-Maternal Immune Interface in Uterus Transplantation.

Publications

The Fetal-Maternal Immune Interface in Uterus Transplantation.

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