دورية أكاديمية
Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs.
العنوان: | Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs. |
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المؤلفون: | Wienke J; Center for Translational Immunology., Brouwers L; Wilhelmina Children's Hospital Birth Center., van der Burg LM; Center for Translational Immunology., Mokry M; Regenerative Medicine Utrecht.; Laboratory of Clinical Chemistry and Hematology, and., Scholman RC; Center for Translational Immunology., Nikkels PG; Department of Pathology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Netherlands., van Rijn BB; Wilhelmina Children's Hospital Birth Center.; Obstetrics and Fetal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands., van Wijk F; Center for Translational Immunology. |
المصدر: | JCI insight [JCI Insight] 2020 Sep 17; Vol. 5 (18). Date of Electronic Publication: 2020 Sep 17. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
مواضيع طبية MeSH: | Adaptation, Physiological*, Fetus/*metabolism , Lymphocytes, Tumor-Infiltrating/*immunology , Neoplasms/*pathology , Placenta/*metabolism , T-Lymphocytes, Regulatory/*immunology , Uterus/*metabolism, Cesarean Section ; Female ; Fetus/immunology ; Humans ; Lymphocytes, Tumor-Infiltrating/metabolism ; Maternal-Fetal Exchange ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Placenta/immunology ; Pregnancy ; T-Lymphocytes, Regulatory/metabolism ; Transcriptome ; Uterus/immunology |
مستخلص: | Tregs are crucial for maintaining maternal immunotolerance against the semiallogeneic fetus. We investigated the elusive transcriptional profile and functional adaptation of human uterine Tregs (uTregs) during pregnancy. Uterine biopsies, from placental bed (materno-fetal interface) and incision site (control) and blood were obtained from women with uncomplicated pregnancies undergoing cesarean section. Tregs and CD4+ non-Tregs were isolated for transcriptomic profiling by Cel-Seq2. Results were validated on protein and single cell levels by flow cytometry. Placental bed uTregs showed elevated expression of Treg signature markers, including FOXP3, CTLA-4, and TIGIT. Their transcriptional profile was indicative of late-stage effector Treg differentiation and chronic activation, with increased expression of immune checkpoints GITR, TNFR2, OX-40, and 4-1BB; genes associated with suppressive capacity (HAVCR2, IL10, LAYN, and PDCD1); and transcription factors MAF, PRDM1, BATF, and VDR. uTregs mirrored non-Treg Th1 polarization and tissue residency. The particular transcriptional signature of placental bed uTregs overlapped strongly with that of tumor-infiltrating Tregs and was remarkably pronounced at the placental bed compared with uterine control site. In conclusion, human uTregs acquire a differentiated effector Treg profile similar to tumor-infiltrating Tregs, specifically at the materno-fetal interface. This introduces the concept of site-specific transcriptional adaptation of Tregs within 1 organ. |
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فهرسة مساهمة: | Keywords: Adaptive immunity; Immunology; Obstetrics/gynecology; Reproductive Biology; T cells |
تواريخ الأحداث: | Date Created: 20200819 Date Completed: 20210531 Latest Revision: 20210531 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC7526557 |
DOI: | 10.1172/jci.insight.137926 |
PMID: | 32809975 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2379-3708 |
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DOI: | 10.1172/jci.insight.137926 |