Immune cells and immune-based therapy in pancreatitis
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IMMUNOLOGY AT STANFORD UNIVERSITY
Immune cells and immune-based therapy in pancreatitis Jing Xue • Vishal Sharma • Aida Habtezion
Published online: 8 April 2014 Ó Springer Science+Business Media New York 2014
Aida Habtezion
Abstract Alcohol and gallstones are the most common etiologic factors in acute pancreatitis (AP). Recurrent AP can lead to chronic pancreatitis (CP). Although the underlying pathophysiology of the disease is complex, immune cells are critical in the pathogenesis of pancreatitis and determining disease severity. In this review, we discuss the role of innate and adaptive immune cells in both AP and CP, potential immune-based therapeutic targets, and animal models used to understand our knowledge of the disease. The relative difficulty of obtaining human pancreatic tissue during pancreatitis makes animal models necessary. Animal models of pancreatitis have been generated to understand disease pathogenesis, test therapeutic interventions, and investigate immune responses. Although current animal models do not recapitulate all aspects of human disease, until better models can be developed available models are useful in addressing key research questions. Differences between experimental and clinical pancreatitis need consideration, and when therapies are tested, models with established disease ought to be included. Keywords
Pancreatitis Immune cells Animal models Immune therapy
Abbreviations AP Acute pancreatitis ANS Anti-neutrophil serum CP Chronic pancreatitis IL Interleukin MCP Monocyte chemotactic protein PSCs Pancreatic stellate cells Th T helper Treg Regulatory T cells TLR Toll-like receptor TNF Tumor necrosis factor
Introduction Premature activation of digestive enzymes in pancreatic acinar cells initiates autodigestion of the pancreas. To date, J. Xue V. Sharma A. Habtezion (&) Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: [email protected]
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studies understanding the fundamental mechanisms of pancreatic enzymatic activation following ductal cell injury or acinar cell damage have led to the mechanistic understanding of intracellular calcium changes and premature activation of intracellular trypsinogen. Acute pancreatitis (AP) also leads to an inflammatory state where researchers have been able to elucidate the role of leukocytes as important players in the pathogenesis of the disease. Recurrent or persistent AP can lead to chronic pancreatitis (CP), a progressive inflammatory and fibrotic disease. CP can eventually lead to irreversible damage and, in late stages, pancreatic exocrine, and endocrine deficiency [1]. Pancreatic stellate cells (PSCs), which can be activated by many triggers including infiltrating leukocytes, play a critical role in fibrogenesis and CP progression [2]. Current treatment of CP is aimed at pain control and addressing exocrine and endocrine dysfunctions. With the discovery of PSCs and understanding of some of the molecular mediators and
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