TRANSCRIPTIONAL CONTROL OF A GUT-ASSOCIATED INFLAMMATORY RESPONSE IN A SIMPLE INVERTEBRATE DEUTEROSTOME

13 Jun 2017
14:15 - 14:30

TRANSCRIPTIONAL CONTROL OF A GUT-ASSOCIATED INFLAMMATORY RESPONSE IN A SIMPLE INVERTEBRATE DEUTEROSTOME

Kate Buckley, George Washington University

Katherine M. Buckley1, Jonathan P. Rast2

1Department of Biological Sciences, George Washington University, Washington, DC
2Department of Immunology and Department of Medical Biophysics, University of Toronto, Toronto, ON

Sea urchin larvae are morphologically simple organisms that share an important genetic heritage with vertebrates, and provide an experimentally tractable system in which to characterize transcriptional control of the gut-associated immune response. In response to seawater exposure to the marine bacterium Vibrio diazotrophicus, larvae exhibit robust changes in cellular behavior and gene activity. Bacteria accumulate in the gut and later invade the body cavity where they are rapidly cleared by a coordinated response of phagocytic and granular immune cells. Peripheral immune cells migrate through the body cavity and accumulate at the gut. Analysis of RNA-Seq data from immune-challenged larvae reveals transcriptional changes in genes with homologs of important vertebrate immune factors, sea urchin-specific response genes and a set of novel genes with homologs that are widely distributed in bilaterians, but absent from vertebrates and ecdysozoans. The most acutely upregulated genes early in this response are two types of IL17 genes. Whole mount in situ hybridization and BAC-based fluorescent protein reporters indicate that these cytokines are expressed within gut epithelial cells. Perturbation of IL17 signaling results in reduced expression of tnfaip3 (a negative feedback inhibitor of IL17), nfkbiz (a vertebrate IL17 target gene), cebpα, cebpγ and soul1. These results indicate that the highly regulated IL17 expression in the gut epithelium and signaling through IL17R1 form a central axis of larval gutassociated immunity. The morphological simplicity of this system provides a model to investigate system-wide molecular interactions at single-cell resolution and to characterize the distributed gene regulatory network that underpins immune response