Impairment of regulatory T cells in patients with neonatal necrotizing enterocolitis

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‑β⁺ 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.