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Infiltrating lymphocytes initiate necrotising enterocolitis

▸ Egan CE, Sodhi CP, Good M, et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest Published Online First: 21 Dec 2015. doi: 10.1172/JCI83356

Necrotising enterocolitis (NEC) is a severe inflammatory disease of the GI tract that occurs in premature infants and can result in death. The pathogenesis of NEC includes a perturbation of the intestinal barrier leading to an inflammatory infiltration into the intestinal mucosa of the host resulting in systemic sepsis. Most studies on the pathophysiology of NEC have focused on the intestinal epithelium being responsible for the disease. The role of intestinal inflammatory cells in NEC has not been well studied. Toll-like receptor (TLR) activation is necessary for NEC development, as it is expressed at significantly higher levels on the intestinal epithelium of the premature murine and human gut. It remains to be elucidated if there is a link between increased TLR4 expression in the premature gut and the inflammatory infiltration that is observed in the intestine in NEC. In this study, Egan and colleagues sought to investigate this potential link in hopes of shedding light on the mechanisms that lead to NEC. The researchers found that the cellular infiltrate in both murine and human NEC contains a high number of CD4+ T cells, specifically CD4+ Th17 cells. Their findings suggest that these infiltrating T cells initiate the disease, as the transfer of NEC-elicited mucosal CD4+ T cells into naive mice spontaneously induced intestinal inflammation, while Rag1-deficient mice were protected from NEC development. When the interleukin 17 (IL-17) receptor was blocked, NEC severity diminished. Collectively, these findings suggest that CD4+ Th17 cell accumulation leads to NEC development, and TLR4 signalling in the intestinal epithelium is needed for the cellular infiltration. From a clinical standpoint, the researchers show that …

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