MR1-deficiency in neonatal mice renders protection from necrotizing enterocolitis

Abstract

Abstract Necrotizing enterocolitis (NEC) is a life-threatening disease that affects ~ 7% of premature neonates. NEC maintains high morbidity/mortality and there are long term sequelae including short bowel syndrome. The risk factors of developing NEC include prematurity, very low birth weight, microbial dysbiosis and infections. Mucosal-associated invariant T (MAIT) cells are innate T cells that have both innate and adaptive immune cell characteristics and are enriched in mucosal tissues, such as intestines. MR1 is the antigen presenting molecule for MAIT cells. Therefore, MR1-knockout (MR1 KO) mice lack MAIT cells. We hypothesized that MR1/MAIT cells play a key role in the development of NEC. To test the hypothesis, NEC was induced in 5-day old B6 wild type (WT) and MR1 KO mouse pups with gavage formula feeds supplemented with LPS as well as exposure to intermittent hypoxia and hypothermia. Pups were assessed daily for clinical sickness scores. Animals were euthanized on postnatal day 9. Intestine segments were harvested and assessed for histological NEC and cytokines were measured using multiplex assay. Compared to WT mice, we found MR1 KO pups did not develop typical NEC symptoms. When compared to WT mice with NEC, MR1 KO mice undergoing the treatment for NEC, had lower clinical scores (WT=4 [3–4]; MR1 KO=0 [0–0], p<0.05) and intestinal histology scores (WT=1.5 [1–2.375]; MR1 KO=0 [0–0.3745], p<0.05). The cytokine profile of the intestines in MR1 KO NEC mice, when compared to those in WT NEC mice, showed significant differences in IL-6 and IL-10 levels. In conclusion, deletion of MR1 in mice appears to be protective in experimental NEC. Future work will focus on studying the role MR1/MAIT cells in NEC disease development.