Single-Cell Insights into Immune Dysregulation and Resistin's Role in Severe Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is an inflammatory disease of the pancreas with an increasing incidence worldwide. While mild AP (MAP) is often easily managed and resolved without complications, severe AP (SAP) is associated with significant morbidity and mortality. However, there remains a lack of effective methods to predict the severity of the disease at the time of initial diagnosis. Despite advances in the understanding of AP, reliable biomarkers for the early prediction of SAP remain unavailable, hindering timely intervention and appropriate treatment. Here, we show that the severity of AP can be predicted by distinct immune responses in peripheral blood mononuclear cells using single-cell RNA sequencing. Our data reveals that an increased myeloid-to-lymphoid ratio and an enhanced RETN-TLR4 axis between myeloid cells are key immunological determinants of SAP. We show that SAP-associated classical monocytes characterized by high RETN expression are immunosuppressive and regulated by STAT3. In addition, SAP exhibits an enhanced classical complement system and increased humoral immune responses during the course of the disease, whereas MAP shows an attenuated immune response for a short period of time. These findings provide new insights into the progression of AP and suggest diagnostic biomarkers and therapeutic targets to mitigate SAP-related immune dysregulation.

Keywords: RESISTIN, Acute pancreatitis, Biomarker, Single-cell RNA sequencing