LAUSR

&NA; Necrotizing enterocolitis (NEC) is a life‐threatening condition that can occur in about 7% of pre‐term infants, and approximately 20% to 30% of the cases will end in death. An overactive immune response is thought to be a primary instigator of many symptoms during NEC. Hence, we hypothesized that NEC patients might present impairment in regulatory T (Treg) cells that limited their capacity to contain the excessive inflammation‐induced damage. To investigate this, peripheral blood mononuclear cells were collected from NEC and non‐NEC infants with matching age and weight. Treg cells, identified as CD3+CD4+CD25+/hiFoxp3+ T cells, were present at significantly lower frequency in NEC infants than in non‐NEC infants. We also observed that the frequency of IL‐17+ CD4+ T cells was significantly higher in NEC infants, while the frequencies of IL‐10+ and TGF‐&bgr;+ CD4+ T cells were significantly lower in NEC infants. The CD4+CD25+/hi Treg cells from NEC infants were capable of suppressing CD4+CD25− T conventional cell proliferation, but with significantly reduced potency than the CD4+CD25+/hi Treg cells from non‐NEC infants. In addition, the CD4+CD25+/hi Treg cells from non‐NEC infants, but not those from NEC infants, were capable of suppressing IL‐17 expression. Furthermore, the CD4+CD25+/hi Treg cells from NEC infants displayed reduced expression of CTLA‐4, LAG‐3, and Helios, compared to those from non‐NEC infants. Overall, these results demonstrated that Treg cells from NEC infants displayed a multitude of functional impairments, and suggested that Treg cells might serve as a treatment target in NEC. HighlightsFrequency of Tregs was significantly lower in NEC infants than in non‐NEC infants.IL‐17+ CD4+ T cells were higher while TGF‐&bgr;+ CD4+ T cells were lower in NEC infants.Tregs from NEC were less capable to suppressing CD4+CD25− Tconv proliferation.Tregs from NEC infants were incapable of suppressing IL‐17 expression.Tregs from NEC infants displayed reduced expression of CTLA‐4, LAG‐3, and Helios.