Passive and adaptive immunity alters enterocyte-specific gene regulation in developing mice

Abstract

Background: Breast-feeding decreases the incidence and seventy of many disorders. It is thought that passive immunity (PI) & the infants own adaptive immunity (AI) play an important role in this process, however, the underlying mechanism of how they protect against these various disorders is poorly understood Objective: We hypothesized that the influence of PI & AI on the regulation of enterocyte specific genes that code for the transport of immunoglobulins, such as plgR & FcI~n, & nutrient processing, such as Ghit5, SGLT1, Lactase & IBAT play a major role in the nrevention of disease. To test the hypothesis, we developed a mouse model where normal'& immunodeficient pups were born & nursed by immunodeficient or normal dams Design/Methods: Mice were immunodeficient, RAG-1 knockouts (ID), or wild type, C57BL6 mice (normal). RNA was isolated from the proximal & distal small intestine & liver throughout weaning. RNA protection assays were then performed with FcRn, plgR, Glut5, Lactase, IBAT & SGLT 1 riboprobes Results: All transcripts studied were developmentally regulated around the time of weaning, & the transcripts in the proximal small intestine had the highest level of expression of the three tissues studied. In normal pups reared in the absence of ~ , the most significant changes from those reared in the presence of P1 were seen in the expression of plgR, which was increased almost 2fold, & a significant decrease in Lactase during the weaning process. When ID pups reared in the presence of PI were compared to normal pups reared in the presence of P1, there were significant decreases in the expression of plgR & Lactase, and also significant increases in expression levels of FcRn, Gfut5 & IBAT during weaning. When ID pups reared in the absence of PI were compared to normal pups reared in the presence of PI, there was a significant decline in expression of plgR & Lactase, & also a significant increase in the expression of IBAT. The expression levels of SGLT1 were not changed significantly by any of the experimental conditions Conclusions: This murine model allows us to simultaneously evaluate the role of passive & adaptive immunity in controlling the expression of enterocytespecific transcripts and altering the various physiologic functions during breast-feeding Finally, we demonstrate that both adaptive & passive immunity influence the developmental expression of genes that may be involved in the protective effect of breast-feeding.