Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities.

ABSTRACT: Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/T_H17 polarization. In murine NEC, pro-inflammatory type 3 NKp46^-RORγt⁺Tbet⁺ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46⁺RORγt⁺ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanist

SUBMITTER: Cho SX 

PROVIDER: S-EPMC7666196 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature