IL-22 Exacerbates Coxsackievirus Type B3-Induced Pancreatitis by Elevating Viral Replication Through STAT3 Activation

Coxsackievirus type B3 (CVB3) is implicated in diseases such as chronic myocarditis and pancreatitis. While IL-22 is known to play complex roles in immune responses during viral infections, its role in CVB3-induced pancreatitis remains unclear. This study examined the impact of IL-22 on pancreatic pathology during CVB3 infection using histological analyses, glucose tolerance tests, immunostaining, viral load quantification, and molecular assays in both mouse pancreatic tissues and HeLa cells. The results demonstrate that IL-22 exacerbates CVB3-induced pancreatitis by promoting viral replication and pancreatic injury. Mechanistically, IL-22 enhances CVB3 replication through recruitment of phosphatidylinositol 4-kinase III beta, mediated by STAT3 activation. These findings reveal a detrimental role for IL-22 in CVB3 infection, characterized by increased apoptosis, β-cell dysfunction, and elevated viral load, providing new insight into the pathogenesis of virus-induced pancreatitis.