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Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+CD4+CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4+ Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-α-producing CD4+ T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.
Pubmed ID: 30770246 RIS Download
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Software R package for sequence alignment and counting for R. Used for analyses of second and third generation sequencing data, for read mapping, read counting, SNP calling, short and long read alignment, quantification and mutation discovery. Includes assessment of sequence reads, read alignment, read summarization, exon-exon junction detection, fusion detection, detection of short and long indels, absolute expression calling and SNP calling. Can be used with reads generated from any of the major sequencing platforms including Illumina GA/HiSeq/MiSeq, Roche GS-FLX, ABI SOLiD and LifeTech Ion PGM/Proton sequencers.
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