Immunity:促进胎儿肠道发育的T细胞,可介导早产儿的肠道炎症
  • 人类胎儿肠道含有生成TNF-α的CD4+CD69+效应记忆T细胞(TEM),在孕早期末尾即存在;
  • 单细胞RNA测序表明这种TEM呈现Th1表型,且介导上皮生长和细胞周期的基因表达上调;
  • 类器官共培养试验显示,当数量少时这种TEM可促进肠上皮发育,数量多时则阻碍肠道干细胞增殖,该作用依赖于TNF-α;
  • 患坏死性小肠结肠炎早产儿的肠道炎症中,这种TEM数量增多,TNF信号增强;
  • TNF-α+CD4+TEM可促进胎儿肠道粘膜发育,但在早产儿中可介导肠道炎症。
主编推荐语
mildbreeze
胎儿的免疫系统通常被认为是具有抗炎的免疫耐受特性,然而早产儿却容易患严重的肠道炎症疾病,比如坏死性小肠结肠炎(NEC)。Immunity近期发表研究,胎儿肠道中存在的一种TNF-α+CD4+T细胞可促进肠上皮发育,而早产可能诱导这种T细胞活化增殖,引起早产儿的肠道炎症,是早产儿易患NEC的潜在机制。
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Immunity [IF:22.553]

Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life

人类胎儿产生TNF-α细胞因子的CD4+效应记忆T细胞促进生命早期的肠道发育并介导炎症

10.1016/j.immuni.2018.12.010

2019-02-12, Article

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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-a (TNF-a) + 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 dosedependent, TNF-a-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-a-producing CD4+ T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.

First Authors:
Martin E Baumdick,Adrian F Sagebiel

Correspondence Authors:
Madeleine J Bunders

All Authors:
Renee RCE Schreurs,Martin E Baumdick,Adrian F Sagebiel,Max Kaufmann,Michal Mokry,Paul L Klarenbeek,Nicola Schaltenberg,Fenja L Steinert,Jorik M van Rijn,Agata Drewniak,Sarah-May ML The,Roel Bakx,Joep PM Derikx,Niek de Vries,Willemijn E Corpeleijn,Steven T Pals,Nicola Gagliani,Manuel A Friese,Sabine Middendorp,Edward ES Nieuwenhuis,Konrad Reinshagen,Teunis BH Geijtenbeek,Johannes B van Goudoever,Madeleine J Bunders

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