Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation

Kurashima, Yosuke; Kigoshi, Takaaki; Murasaki, Sayuri; Arai, Fujimi; Shimada, Kaoru; Seki, Natsumi; Hase, Koji; Ohno, Hiroshi; Kawano, Kazuya; Ashida, Hiroshi; Suzuki, Toshihiko; Morimoto, Masako; Saito, Yukinobu; Sasou, Ai; Goda, Yuki; Yuki, Yoshikazu; Inagaki, Yutaka; Iijima, Hideki; Suda, Wataru; Hattori, Masahira; Kiyono, Hiroshi

doi:10.1038/s41467-021-21277-2

Cited by 44 publications

(81 citation statements)

References 79 publications

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“…The GP2, secreted by pancreatic cells, is expressed on M cells located in the small intestine and initiates antigen-specific mucosal immune responses that control bacterial invasion into intestinal epithelial cells. In a chemically induced colitis in mice, an increase of GP2 expression in the pancreas has been observed, which has been an effect of enhanced production of pro-inflammatory cytokines such as TNF [ 51 ]. The significant increase of luminal GP2 level was also reported in patients with CD.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the role the autoantibodies in the pathogenesis of pancreatic diseases in IBD is still unknown. Interestingly, elevated serum GP2 levels were noted in patients with pancreatitis and in CD patients [ 51 , 52 ]. Involvement of the pancreas in IBD may be connected with GP2 dysfunction or an increased level of anti-GP2 autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

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Pancreatic Disorders in Children with Inflammatory Bowel Disease

et al. 2021

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Background and Objectives: Inflammatory bowel disease (IBD) is a chronic condition and mainly affects the intestines, however, the involvement of the other organs of the gastrointestinal tract (upper part, pancreas, and liver) have been observed. The coexistence of IBD with pancreatic pathology is rare, however, it has been diagnosed more frequently during recent years in the pediatric population. This article reviews the current literature on the most common pancreatic diseases associated with IBD in the pediatric population and their relationship with IBD activity and treatment. Materials and Methods: We performed a systematic review of data from published studies on pancreatic disorders, also reported as extraintestinal manifestations (EIMs), among children with IBD. We searched PubMed and Web of Science to identify eligible studies published prior to 25 April 2020. Results: Forty-four papers were chosen for analysis after a detailed inspection, which aimed to keep only the research studies (case control studies and cohort studies) or case reports on children and only those which were written in English. The manifestations of IBD-associated pancreatic disorders range from asymptomatic increase in pancreatic enzymes activity to severe disease such as acute pancreatitis. Acute pancreatitis (AP) induced by drugs, mainly thiopurine, seems to be the most- often-reported pancreatic disease associated with IBD in children. AP associated with other than drug etiologies, and chronic pancreatitis (CP), are rarely observed in the course of pediatric IBD. The pancreatic involvement can be strictly related to the activity of IBD and can also precede the diagnosis of IBD in some pediatric patients. The course of AP is mild in most cases and may occasionally lead to the development of CP, mainly in cases with a genetic predisposition. Conclusions: The involvement of the pancreas in the course of IBD may be considered as an EIM or a separate co-morbid disease, but it can also be a side effect of IBD therapy, therefore a differential diagnosis should always be performed. As the number of IBD incidences with concomitant pancreatic diseases is constantly increasing in the pediatric population, it is important to include pancreatic enzymes level measurement in the workup of IBD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pancreatic Disorders in Children with Inflammatory Bowel Disease

et al. 2021

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“…Its pivotal role as a first line of defense against adhesive and invasive commensal bacteria has been confirmed by recently published results on glycoprotein 2 (GP2) [ 47 ]. GP2 is the most abundant pancreatic membrane protein of zymogen granule and is also expressed on microfold cells (M cells) located in the small intestine [ 47 ]. It initiates antigen-specific mucosal immune responses against bacterial invasion into intestinal epithelial cells.…”

Section: Role Of Genetics In Pediatric Pancreatitis and Its Association With Ibdmentioning

confidence: 95%

“…Such a close interaction between changes of microbiota, intestinal inflammation and pancreatic disease has been considered as the gut-pancreas axis [23]. Its pivotal role as a first line of defense against adhesive and invasive commensal bacteria has been confirmed by recently published results on glycoprotein 2 (GP2) [47]. GP2 is the most abundant pancreatic membrane protein of zymogen granule and is also expressed on microfold cells (M cells) located in the small intestine [47].…”

Section: Role Of Genetics In Pediatric Pancreatitis and Its Association With Ibdmentioning

confidence: 99%

“…IBD has been associated consistently with gut dysbiosis, low concentration of Firmicutes, such as Bifidobacterium, Clostridia and especially Faecalibacterium prausnitzii, and increased concentrations of Escherichia Coli [ 46 ]. Adherent-invasive E. coli are resistant to clearance by the immune system and induce an increased expression of the inflammatory cytokine tumor necrosis factor-α (TNF), which is fundamental for the onset and progression of gut inflammation [ 47 ]. Similarly, in AP and CP levels of Bifidobacterium or Lactobacillus have been shown to be lower, along with a higher concentration of Enterobacteriaceae.…”

Section: Role Of Genetics In Pediatric Pancreatitis and Its Association With Ibdmentioning

confidence: 99%

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Pancreatic Associated Manifestations in Pediatric Inflammatory Bowel Diseases

Cucinotta

Romano

Dipasquale

2021

Genes

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Inflammatory bowel diseases (IBDs) are chronic relapsing inflammatory conditions of the gastrointestinal tract, encompassing Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U). They are currently considered as systemic disorders determined by a set of genetic predispositions, individual susceptibility and environmental triggers, potentially able to involve other organs and systems than the gastrointestinal tract. A large number of patients experiences one or more extraintestinal manifestations (EIMs), whose sites affected are mostly represented by the joints, skin, bones, liver, eyes, and pancreas. Pancreatic abnormalities are not uncommon and are often underestimated, encompassing acute and chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency and asymptomatic elevation of pancreatic enzymes. In most cases they are the result of environmental triggers. However, several genetic polymorphisms may play a role as precipitating factors or contributing to a more severe course. The aim of this paper is to provide an updated overview on the available evidence concerning the etiology, pathogenesis and clinical presentation of pancreatic diseases in IBD pediatric patients.

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Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas–intestinal barrier axis

et al. 2022

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The pancreas contains exocrine glands, which release enzymes (e.g., amylase, trypsin, and lipase) that are important for digestion and islets, which produce hormones. Digestive enzymes and hormones are secreted from the pancreas into the duodenum and bloodstream, respectively. Growing evidence suggests that the roles of the pancreas extend to not only the secretion of digestive enzymes and hormones but also to the regulation of intestinal homeostasis and inflammation (e.g., mucosal defense to pathogens and pathobionts). Organ crosstalk between the pancreas and intestine is linked to a range of physiological, immunological, and pathological activities, such as the regulation of the gut microbiota by the pancreatic proteins and lipids, the retroaction of the gut microbiota on the pancreas, the relationship between inflammatory bowel disease, and pancreatic diseases. We herein discuss the current understanding of the pancreas-intestinal barrier axis and the control of commensal bacteria in intestinal inflammation.

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Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation

Cited by 44 publications

References 79 publications

Pancreatic Disorders in Children with Inflammatory Bowel Disease

Pancreatic Disorders in Children with Inflammatory Bowel Disease

Pancreatic Associated Manifestations in Pediatric Inflammatory Bowel Diseases

Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas–intestinal barrier axis

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