Monocyte activation and inflammation can exacerbate Treg/Th17 imbalance in infants with neonatal necrotizing enterocolitis

• Published in: International immunopharmacology Vol. 59; pp. 354 - 360
• Main Authors: Pang, Yin, Du, Xiaoya, Xu, Xueli, Wang, Mengjie, Li, Zhichang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2018; Elsevier BV
• Subjects: CD4 antigen; Cell activation; Cytokines; Differentiation; Enterocolitis; Foxp3 protein; Helper cells; Immune system; Infants; Inflammation; Interleukin 10; Interleukin 6; Intestine; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Monocyte; Monocytes; Necrotizing enterocolitis; Neonatal care; Neonatal necrotizing enterocolitis; Neonates; Organs; Patients; TLR4 protein; Toll-like receptors; Treg; Tumor necrosis factor-α; Monocyte; Neonatal necrotizing enterocolitis; Treg
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2018.04.026

Necrotizing enterocolitis (NEC) is a potentially fatal disease that develops in the intestinal tract of newborn infants. An overactive immune system in the intestinal tract of NEC patients not only propagates inflammation and mediates tissue damage, but may also radiate the disease systemically and impose injury to distant organs. We previously identified impairment in the Treg compartment in NEC patients. Here, we hypothesized that monocytes, which could promote iTreg differentiation both in vitro and in vivo, were dysregulated in NEC infants. In age-, sex-, and weight-matched NEC infants and healthy control infants, the monocytes from PBMCs were investigated. Monocytes from NEC infants presented significantly higher TLR4 expression. With or without LPS stimulation, monocytes from NEC infants presented elevated TNF-α and IL-6 expression, together with reduced expression of TGF-β. When incubated with autologous CD4+ T cells, monocytes from NEC infants preferentially promoted the differentiation of RORγt-expressing Th17 cells, but not Foxp3-expressing Treg cells. However, using exogenous TGF-β and IL-10, the development of Foxp3 expression could be significantly elevated. Together, these results demonstrate that monocytes in NEC patients displayed a proinflammatory profile that might contribute to the production of proinflammatory cytokines and the suppression of Treg cells. •Monocytes from NEC infants presented significantly higher TLR4 expression.•Monocytes from NEC showed elevated TNF-α and IL-6 and reduced TGF-β expression.•Monocytes from NEC preferentially promoted the differentiation of Th17 cells.•Monocytes from NEC could promote Treg differentiation through TGF-β and IL-10.