To our knowledge, our report is the first demonstrating that PGRN activates CD4+ T helper cells in the large intestine and induces IL-22-associated repair pathways that protect from CDI-mediated epithelial barrier damage, which may serve as a therapeutically important pathway that maintains integrity of the intestinal barrier and reduces mortality during CDI (Figure 7g). This evidence concerns the gene CD4 and clostridium difficile infection.