Abstract
The inflammatory response in acute pancreatitis (AP) is associated with acinar-to-dendritic cell transition. The CD4+ T-cell-mediated adaptive immune response is necessary for pancreatic inflammatory damage. However, the effect of acinar-to-dendritic cell transition on the CD4+ T-cell response and the regulatory mechanism remain undefined. A mouse animal model of AP was established by repeated intraperitoneal injection of CAE. The mTOR inhibitor rapamycin was administered before AP induction. Primary acinar cells were isolated and co-incubated with subsets of differentiated CD4+ T cells. The expression of DC-SIGN was also assessed in pancreatic tissues from human AP patients. We found acinar cells expressed DC-SIGN and displayed the phenotype of dendritic cells (DCs), which promoted the differentiation of naive CD4+ T cells into CD4+/IFN-γ+ Th1 and CD4+/IL-17A+ Th17 cells in pancreatic tissues during AP. DC-SIGN was the target gene of Myc. The mTOR inhibitor rapamycin inhibited AP-induced DC-SIGN expression, CD4+ Th1/Th17 cell differentiation and the pro-inflammatory response via Myc. Acinar cells expressed DC-SIGN in pancreatic tissues of human patients with AP. In conclusion, acinar-to-dendritic cell transition is implicated in the CD4+ T-cell immune response via mTOR-Myc-DC-SIGN axis, which might be an effective target for the prevention of local pancreatic inflammation in AP.
Highlights
Acute pancreatitis (AP), triggered by the activation of digestive enzymes in acinar cells, is a clinical cause of acute abdomen[1,2]
haematoxylin and eosin (HE) staining of pancreatic tissues revealed that oedema and inflammatory infiltration gradually intensified as AP developed (Fig. 1a, b)
Increasing numbers of studies have focused on the role of acinar cells in the initiation of local pancreatic inflammation during AP43,44
Summary
Acute pancreatitis (AP), triggered by the activation of digestive enzymes in acinar cells, is a clinical cause of acute abdomen[1,2]. Up to 20% of cases progress to severe AP (SAP), which has a high mortality rate and is associated with pancreatic necrosis, systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction[5,6]. It has been demonstrated to be implicated in DC migration, T-cell differentiation and pathogen immune escape[12,13,14]. Accumulating evidence from studies indicates that DC-SIGN is expressed on gastric epithelial cells, intestinal epithelial cells and tubular epithelial cells, which induces epithelial-DC transdifferentiation and initiates naive CD4+ T-cell differentiation[15,16,17]. Our previous study suggested that AP induces significant upregulation of DC-SIGN in acinar cells, which is associated with the immune response in AP patients, yet the mechanism remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
