دورية أكاديمية
أعرض في EDS

A disrupted FOXP3 transcriptional signature underpins systemic regulatory T cell insufficiency in early pregnancy failure.

التفاصيل البيبلوغرافية
العنوان: A disrupted FOXP3 transcriptional signature underpins systemic regulatory T cell insufficiency in early pregnancy failure.
المؤلفون: Moldenhauer LM; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Foyle KL; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Wilson JJ; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Wong YY; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Sharkey DJ; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Green ES; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Barry SC; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia., Hull ML; Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia., Robertson SA; Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, SA, Australia.
المصدر: IScience [iScience] 2024 Jan 23; Vol. 27 (2), pp. 108994. Date of Electronic Publication: 2024 Jan 23 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Regulatory T (Treg) cell defects are implicated in disorders of embryo implantation and placental development, but the origins of Treg cell dysfunction are unknown. Here, we comprehensively analyzed the phenotypes and transcriptional profile of peripheral blood Treg cells in individuals with early pregnancy failure (EPF). Compared to fertile subjects, EPF subjects had 32% fewer total Treg cells and 54% fewer CD45RA + CCR7 + naive Treg cells among CD4 + T cells, an altered Treg cell phenotype with reduced transcription factor FOXP3 and suppressive marker CTLA4 expression, and lower Treg:Th1 and Treg:Th17 ratios. RNA sequencing demonstrated an aberrant gene expression profile, with upregulation of pro-inflammatory genes including CSF2 , IL4 , IL17A , IL21 , and IFNG in EPF Treg cells. In silico analysis revealed 25% of the Treg cell dysregulated genes are targets of FOXP3. We conclude that EPF is associated with systemic Treg cell defects arising due to disrupted FOXP3 transcriptional control and loss of lineage fidelity.
Competing Interests: The authors declare no competing interests.
(© 2024 The Author(s).)
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فهرسة مساهمة: Keywords: Health sciences; Immunology; Pregnancy
تواريخ الأحداث: Date Created: 20240208 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10847744
DOI: 10.1016/j.isci.2024.108994
PMID: 38327801
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2024.108994