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Grant Abstract

Grant Number: 2R01DK041479-23
PI Name: Ross
Project Title: Retinoid Nutritional Status and Immune Function

Abstract: DESCRIPTION (provided by applicant): At birth, the concentrations of vitamin A (retinol) in liver and plasma are much lower than in older children and well-fed adults. Vitamin A may therefore be a rate-limiting nutrient at this life stage. This application focuses on the interactin in early life of vitamin A supplementation and immune function. Our central hypothesis is: Improving vitamin A nutritional status in vitamin A-marginal neonates through vitamin A supplementation will increase the antibody response to immunization and promote a successful response to respiratory infection. Reciprocally, pneumonia will alter the ability of the neonate to store and mobilize retinol, which is required throughout the body for retinoid production, and thus for normal immunity and lung development. Currently, scientific evidence for vitamin A supplementation in neonates is very limited. We will use a neonatal mouse model to test whether vitamin A supplementation early in life, combined with immunization, regulates the lung's innate and adaptive immune response to S. pneumoniae infection. Reciprocally, infection may affect the transport and metabolism of vitamin A, which is hypothesized due to reduced hepatic production of retinol-binding protein, RBP. Our specific aims address both the response to infection and infection-induced alterations in retinol metabolism. The outcome of this research will be a better understanding of neonatal retinol metabolism and utilization of vitamin A in early life, which is expected to help make better public health decisions regarding early life vitamin A supplementation. PUBLIC HEALTH RELEVANCE: A nutritional deficiency of vitamin A deficiency impairs immune response, which in turn increases severity of infectious diseases. Although vitamin A supplementation is now widely used in international health programs to improve survival in young children, little is known about vitamin A and immunity in the neonatal period. Building on our previous studies, we propose to investigate vitamin A supplementation and antibody production, relevant to lung health in humans, in a neonatal mouse model. Evidence gained from our basic studies is expected to fill gaps in knowledge concerning the role of vitamin A in neonatal and young child health.

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