550a Loss of PTPN22 Regulates MDP Induced Signaling, Cytokine Release, Autophagy and Inflammasome Activation

Abstract

effect of early exposure on neonatal development is unknown. Here we focused on early exposure to PM since children and young adults are most commonly affected with IBD. Our aim was to study the effect of airborne PM on developing intestine in the IL-10-/colitis model, and if chronic exposure during the neonatal period would alter disease development and/or have long-lasting effects that would alter gut responses to injury in later life. Methods: IL-10-/pregnant dams and pups were fed mouse chow with/without PM (9μg/g) and pups were studied at 10 and 14 weeks of age. At 20 weeks of age, mice were subjected to 2% DSS in drinking water for 5 days followed by 2 days recovery. Homogenates from mesenteric lymph nodes (MLN) were cultured to measure bacterial translocation. To examine mucosal immune function, segments of small and large intestines were homogenized for cytokine analysis via MesoScale discovery platform. Results: PM exposure had no effect on mouse weight gain but did increase colonic pro-inflammatory cytokine expression at 10 and 14 weeks of age (Table). However, IL-17 levels were reduced in PM-fed mice at 10 weeks but did increase by 14 weeks when compared to age-matched controls. In addition, increased levels of bacterial translocation into MLN were seen at 10 weeks. By 20 weeks, PM-fed mice showed changes in the small intestine with decreased IL-1 β but increased TNFα and IFNγ, suggesting changes in both innate and adaptive immunity. PM-fed mice responded to DSS treatment with increased colonic TNFα and IL-1β compared with non-PM fed mice. In addition, there were increased numbers of live bacteria in the MLN of DSS treated PM-fed mice compared to DSS treated control chow-fed mice. Conclusions: IL-10-/neonatal mice exposed to PM had an increased bacterial translocation and earlier onset of inflammatory disease. Continual exposure into adulthood resulted in small intestinal inflammation and a reduction in bacterial killing capacity in the MLN. Our data suggests that early exposure to air pollution particulates can result in an earlier onset of intestinal disease in geneticallysusceptible hosts and can alter responses to gut injury in later life. Cytokine Expression Levels in the Colon