Identification of regulatory genes through global gene expression analysis of aHelicobacter pylorico-culture system

Helicobacter pylori is a gram-negative bacterium that establishes life-long infections by inducing immunoregulatory responses. We have developed a novel ex vivo H. pylori co-culture system to identify new regulatory genes based on expression kinetics overlapping with that of genes with known regulatory functions. Using this novel experimental platform, in combination with global transcriptomic analysis, we have identified five lead candidates, validated them using mouse models of H. pylori infection and in vitro co-cultures under pro-inflammatory conditions. Plexin domain containing 2 (Plxdc2) was selected as the top lead immunoregulatory target. Gene silencing and ligand-induced activation studies confirmed its predicted regulatory function. Our integrated bioinformatics analyses and experimental validation platform has enabled the discovery of new immunoregulatory genes. This pipeline can be used for the identification of genes with therapeutic applications for treating infectious, inflammatory, and autoimmune diseases.