دورية أكاديمية
Differences in H3K4me3 and chromatin accessibility contribute to altered T-cell receptor signaling in neonatal naïve CD4 T cells.
| العنوان: | Differences in H3K4me3 and chromatin accessibility contribute to altered T-cell receptor signaling in neonatal naïve CD4 T cells. |
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| المؤلفون: | Bermick JR; Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, IA, USA.; Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, Ann Arbor, MI, USA., Issuree P; Department of Internal Medicine, University of Iowa, Iowa City, IA, USA., denDekker A; Department of Vascular Surgery, Michigan Medicine, Ann Arbor, MI, USA., Gallagher KA; Department of Vascular Surgery, Michigan Medicine, Ann Arbor, MI, USA., Santillan D; Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA., Kunkel S; Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA., Lukacs N; Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.; Mary H. Weiser Food Allergy Center, Michigan Medicine, Ann Arbor, MI, USA., Schaller M; Department of Pathology, Michigan Medicine, Ann Arbor, MI, USA.; Pulmonary, Critical Care & Sleep Medicine, University of Florida, Gainesville, FL, USA. |
| المصدر: | Immunology and cell biology [Immunol Cell Biol] 2022 Aug; Vol. 100 (7), pp. 562-579. Date of Electronic Publication: 2022 Jun 20. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 8706300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1711 (Electronic) Linking ISSN: 08189641 NLM ISO Abbreviation: Immunol Cell Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2018- : [Hoboken, NJ] : Wiley Original Publication: [Adelaide, South Australia] : University of Adelaide, [c1987- |
| مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes* , Chromatin*/metabolism, Adult ; Histones ; Humans ; Infant, Newborn ; Lymphocyte Activation/genetics ; Receptors, Antigen, T-Cell/metabolism ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | Neonatal CD4 + T cells have reduced or delayed T-cell receptor (TCR) signaling responses compared with adult cells, but the mechanisms underlying this are poorly understood. This study tested the hypothesis that human neonatal naïve CD4 + TCR signaling and activation deficits are related to differences in H3K4me3 patterning and chromatin accessibility. Following initiation of TCR signaling using anti-CD3/anti-CD28 beads, adult naïve CD4 + T cells demonstrated increased CD69, phospho-CD3ε and interleukin (IL)-2, tumor necrosis factor-α (TNF-α), interferon-γ and IL-17A compared with neonatal cells. By contrast, following TCR-independent activation using phorbol myristate acetate (PMA)/ionomycin, neonatal cells demonstrated increased expression of CD69, IL-2 and TNF-α and equivalent phospho-ERK compared with adult cells. H3K4me3 chromatin immunoprecipitation-sequencing (ChIP-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed on separate cohorts of naïve CD4 + T cells from term neonates and adults, and RNA-seq data from neonatal and adult naïve CD4 + T cells were obtained from the Blueprint Consortium. Adult cells demonstrated overall increased chromatin accessibility and a higher proportion of H3K4me3 sites associated with open chromatin and active gene transcription compared with neonatal cells. Adult cells demonstrated increased mRNA expression of the TCR-associated genes FYN, ITK, CD4, LCK and LAT, which was associated with increased H3K4me3 at the FYN and ITK gene loci and increased chromatin accessibility at the CD4, LCK and LAT loci. These findings indicate that neonatal TCR-dependent defects in activation are epigenetically regulated and provide a potentially targetable mechanism to enhance neonatal CD4 + T-cell responses. (© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.) |
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| معلومات مُعتمدة: | R01 AI141673 United States AI NIAID NIH HHS; R01 HD089940 United States HD NICHD NIH HHS; UL1 TR002537 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: ATAC-seq; ChIP-seq; T-cell receptor; T cell; epigenetics; neonate |
| المشرفين على المادة: | 0 (Chromatin) 0 (Histones) 0 (Receptors, Antigen, T-Cell) 0 (Tumor Necrosis Factor-alpha) 0 (histone H3 trimethyl Lys4) |
| تواريخ الأحداث: | Date Created: 20220524 Date Completed: 20220803 Latest Revision: 20240211 |
| رمز التحديث: | 20240211 |
| مُعرف محوري في PubMed: | PMC9357221 |
| DOI: | 10.1111/imcb.12561 |
| PMID: | 35608955 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1440-1711 |
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| DOI: | 10.1111/imcb.12561 |