Scholarlink

<p>Mechanisms underlying paediatric acute respiratory distress syndrome (PARDS) remain poorly understood, limiting advances in diagnosis and treatment. To address this, we conduct a high-dimensional, multi-omics analysis of paired pulmonary and blood samples from children with PARDS and age-matched controls. Our approach includes transcriptomics, proteomics, flow and mass cytometry, and single-cell RNA sequencing, with further validation using cytokine assays and in vitro models. Severe PARDS is characterised by three convergent immune abnormalities; Pulmonary CD8 <sup>+</sup> T cells display an interferon-driven cytotoxic profile, with exhaustion and apoptosis genes; Pulmonary T cells and myeloid cells exhibit strong interferon-stimulated gene expression; Distinct macrophage subsets show high interferon but suppressed IL-1 pathway genes, associated with impaired leukocyte chemotaxis, phagocytosis, and M1-polarization. This is mirrored by reduced pulmonary IL-1α/β and elevated IFN-γ. The systemic IL-1 signature is similarly dampened, while interferon responses are compartmentalised to the lung. Using an in vitro model, IFN-γ priming is shown to suppress TLR7-induced IL-1 β production through transcriptional inhibition of downstream inflammatory pathways, recapitulating the immune signature observed in patients. Our results reveal interferon-driven immune dysregulation and IL-1 suppression as central features of severe PARDS, highlighting parallels and differences from adult ARDS and underscoring the need for paediatric-specific therapeutic strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A high dimensionality approach reveals immunopathogenic responses driving severe pediatric acute respiratory distress syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

查看全文
  • Judith Ju Ming Wong,
  • Herng Lee Tan,
  • Clare Wei Tian Foo,
  • Nicholas Kim Huat Khoo,
  • Yik-Lam Cho,
  • Su Li Poh,
  • Martin Wasser,
  • Sharifah Hazirah,
  • Jing Yao Leong,
  • Yee Hui Mok,
  • Daryl Zhang Wei Lee,
  • Pavanish Kumar,
  • Joo Guan Yeo,
  • Sylvie Alonso,
  • Salvatore Albani

摘要

Mechanisms underlying paediatric acute respiratory distress syndrome (PARDS) remain poorly understood, limiting advances in diagnosis and treatment. To address this, we conduct a high-dimensional, multi-omics analysis of paired pulmonary and blood samples from children with PARDS and age-matched controls. Our approach includes transcriptomics, proteomics, flow and mass cytometry, and single-cell RNA sequencing, with further validation using cytokine assays and in vitro models. Severe PARDS is characterised by three convergent immune abnormalities; Pulmonary CD8 + T cells display an interferon-driven cytotoxic profile, with exhaustion and apoptosis genes; Pulmonary T cells and myeloid cells exhibit strong interferon-stimulated gene expression; Distinct macrophage subsets show high interferon but suppressed IL-1 pathway genes, associated with impaired leukocyte chemotaxis, phagocytosis, and M1-polarization. This is mirrored by reduced pulmonary IL-1α/β and elevated IFN-γ. The systemic IL-1 signature is similarly dampened, while interferon responses are compartmentalised to the lung. Using an in vitro model, IFN-γ priming is shown to suppress TLR7-induced IL-1 β production through transcriptional inhibition of downstream inflammatory pathways, recapitulating the immune signature observed in patients. Our results reveal interferon-driven immune dysregulation and IL-1 suppression as central features of severe PARDS, highlighting parallels and differences from adult ARDS and underscoring the need for paediatric-specific therapeutic strategies.