生物
免疫学
炎症
肿瘤坏死因子α
细胞因子
T细胞
免疫系统
坏死性小肠结肠炎
胎儿
效应器
人口
记忆T细胞
内科学
医学
环境卫生
遗传学
怀孕
作者
Renée R. C. E. Schreurs,Martin Baumdick,Adrian F. Sagebiel,Max Kaufmann,Michal Mokrý,Paul L. Klarenbeek,Nicola Schaltenberg,Fenja L Steinert,Jorik M. van Rijn,Agata Drewniak,Roel Bakx,Joep P. M. Derikx,Niek de Vries,Willemijn E. Corpeleijn,Steven T. Pals,Nicola Gagliani,Manuel A. Friese,Sabine Middendorp,Edward E. S. Nieuwenhuis,Konrad Reinshagen,Teunis B. H. Geijtenbeek,Johannes B. van Goudoever,Madeleine J. Bunders
出处
期刊:Immunity
[Elsevier]
日期:2019-02-01
卷期号:50 (2): 462-476.e8
被引量:143
标识
DOI:10.1016/j.immuni.2018.12.010
摘要
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.
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