Distinct immune characteristics distinguish hereditary and idiopathic chronic pancreatitis.
The Journal of clinical investigation
Immunology of pancreatitis and environmental factors
CURRENT OPINION IN GASTROENTEROLOGY
2017; 33 (5): 383–89
Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease. Despite numerous animal model studies, questions remain about local immune characteristics in human CP. We profiled pancreatic immune cell characteristics in control organ donors and CP patients that included hereditary and idiopathic CP undergoing total pancreatectomy with islet auto-transplantation. Flow cytometric analysis revealed a significant increase in the frequency of CD68+ macrophages in idiopathic CP. In contrast, hereditary CP showed a significant increase in CD3+ T cell frequency, which prompted us to investigate the T cell receptor beta (TCRbeta) repertoire in CP and controls. TCRbeta-sequencing revealed a significant increase in TCRbeta repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in Vbeta-Jbeta gene family usage between hereditary and idiopathic CP and a positive correlation of TCRbeta rearrangements with disease severity scores. Immunophenotyping analyses in hereditary and idiopathic CP pancreata indicate differences in innate and adaptive immune responses, which highlights differences in immunopathogenic mechanism of disease among subtypes of CP. TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis providing new insights into immune responses associated with human CP.
View details for DOI 10.1172/JCI134066
View details for PubMedID 32053120
This report reviews recent aspects of pancreatitis immunology and environmental factors that link to development and progression of disease.Limited human and animal model studies have recently attempted to understand immune mechanisms that lead to the pathogenesis of acute and chronic pancreatitis. Based on these studies innate immune responses emerge as critical elements in disease pathogenesis and severity of inflammation. The immune basis for environmental factors such as smoking, which are highly associated with disease progression highlight novel cross talk mechanisms between immune and nonimmune pancreatic cells such as the pancreatic stellate cells.Better understanding of immune responses and signaling pathways are emerging as important contributors in pancreatitis development and progression. Such mechanisms are likely to offer future targetable therapies that can either halt or reverse disease progression.
View details for PubMedID 28682796