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Date of Award

Spring 2011

Author's School

College of Arts & Sciences

Author's Department/Program

Biology

Abstract

Dendritic cells (DCs) play a key role in the mucosal immune response, activating and inducing gut-homing in naïve T Cells, and inducing class switch in naïve B Cells. These actions are mediated in great part by signaling via retinoids—Vitamin A derivatives produced from dietary beta-carotene and/or retinyl esters. The importance of Vitamin A has long been established, but only recently have DCs been identified as important to its processing. In this study, we demonstrate that DCs isolated from the lamina propria of mice express a range of proteins necessary for the interconversion and processing of various retinoids and that they do indeed demonstrate these abilities in vitro and in vivo. Among DCs, it was a particular subset characterized by the expression of CD103+ that demonstrated this retinoid-processing capacity. These CD103+ DCs were shown to be the subset involved in B cell class switch to become IgA producing plasma cells and their retinoid-processing ability was shown to be augmented with retinoid treatment at both the gene and functional levels. CRBPII and RALDH2 were identified as two key proteins necessary for this RA processing. We also identified β7 integrin as necessary for DC migration to the intestinal epithelium; the expression of this integrin is known to be selectively imprinted through RA signaling. Our results illustrate that CD103+ DCs are a key player in Vitamin A processing in the intestine and that retinoids are important to their function in promoting the adaptive immune response.

Language

English (en)