Regulatory B10 cells play a protective role in severe acute pancreatitis

Qiu, Zhaoyan; Yu, Pengfei; Bai, Bin; Hao, Yiming; Wang, Shi-qi; Zhao, Zhanwei; Hang, Zhenning; Wang, Qian; Guo, Min; Feng, Qiang; Zhao, Qingchuan

doi:10.1007/s00011-016-0947-9

Cited by 13 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regulatory B cells suppress immune responses via the release of IL-10 or TGF-β, the inhibition of the release of IFN-γ and TNF-α and the induction of Tregs populations as well as interaction with target cells via molecules expressed on the cell surface, such as CD80, CD86 [ 18 , 26 – 30 ]. But our study showed a significant reduction in lymphocytes, CD19 + , B10 and CD19 + CD24 hi CD27 hi cells in AP patients, which was consistent with the results reported by Qiu et al [ 31 ]. Further, we detected lower MFI of CD80 and CD86 on B10 and CD19 + CD24 hi CD27 hi cells in patients with AP and CD19 + CD24 hi CD27 hi cells from AP patients suppressed the cytokine productions of CD4 + T cells and CD14 + monocytes, but the ability of CD19 + CD24 hi CD27 hi cells to induce Tregs response were impaired.…”

Section: Discussionsupporting

confidence: 93%

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease

Qiu

Zhou

et al. 2018

Oncotarget

View full text Add to dashboard Cite

Early stratification of the severity of acute pancreatitis (AP) is clinically important. Regulatory B cells have been found to be associated with disease activity of autoimmune diseases. However, the role of Regulatory B cells in AP remains unknown. We investigate the dynamic longitudinal changes in circulating IL-10-producing B cells (B10) and memory CD19+CD24hiCD27hi cells in patients with AP to evaluate their prediction utility for AP severity. B10, CD19+CD24hiCD27hi cells, inflammatory markers and cytokines were detected in patients with AP immediately after admission to the hospital (day 1), then on the third and seventh days. We observed decreases in lymphocytes, CD19+, B10, CD19+CD24hiCD27hi cells and lower mean fluorescence intensity (MFI) of CD80 and CD86 on B10 or CD19+CD24hiCD27hi cells in patients with AP, especially in those with severe acute pancreatitis (SAP). CD19+CD24hiCD27hi cells from patients with AP suppressed the cytokine productions of CD4+ T cells and CD14+ monocytes, but had impaired ability to induce regulatory T cells response. B10 and CD19+CD24hiCD27hi cells significantly increased in patients with mild acute pancreatitis (MAP) from day 1 to day 7, whereas these indexes remained stable in patients with SAP. B10 or CD19+CD24hiCD27hi cells were negatively correlated with the severity index (APACHE II score), inflammatory markers (C-reactive protein, CD64 index), and cytokines (IL-6, IL-17, TNF-α). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that B10 and CD19+CD24hiCD27hi cells could predict the development of SAP. Thus, the detection of B10 and CD19+CD24hiCD27hi cells may be a practical way to improve the early assessment of AP severity.

show abstract

Section: Discussionsupporting

confidence: 93%

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease

Qiu

Zhou

et al. 2018

Oncotarget

View full text Add to dashboard Cite

show abstract

“…ANP is a severe and emergent disease with multiple complications and a high mortality rate of 7% to 15%[1]. Intestinal barrier dysfunction is now considered as a major reason for the complications such as bacteria translocation and MODS in ANP.…”

Section: Discussionmentioning

confidence: 99%

“…Acute necrotizing pancreatitis (ANP) is a serious systemic disease with a mortality of 7% to 15% [1]. The intestinal barrier dysfunction plays a pivotal role in the development of ANP.…”

Section: Introductionmentioning

confidence: 99%

Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats

et al. 2017

View full text Add to dashboard Cite

ObjectivesIntestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP.MethodsRats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence.ResultsANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1β and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme.ConclusionThe disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.

show abstract

“…While some studies suggest that tumor-infiltrating B cells have a protective role against disease progression [ 7 – 12 ], other studies suggest that Bregs are upregulated in patients with solid tumor malignancies and are associated with enhanced tumor-aggressiveness and poorer prognosis [ 13 – 25 ]. In human lymphoid malignancies, malignant B cells appear to act as Bregs by suppressing the anti-tumor cellular immune response through expression of suppressive ligands [ 26 – 29 ]. This has led to successful targeting of B-regulatory functions of malignant B cells in lymphomas, which have thus far shown remarkably favorable outcomes in several clinical trials [ 26 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

B cell regulation of the anti-tumor response and role in carcinogenesis

Schwartz

Zhang

Rosenblatt

2016

j. immunotherapy cancer

204

168

View full text Add to dashboard Cite

The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses. Multiple murine tumor models exhibit decreased tumor growth in B cell deficient or B cell depleted mice. In several of these models, B cells inhibit T cell mediated tumor immunity and/or facilitate conversion of T cells to CD4+CD25+FoxP3+ T regs, which act to attenuate the innate and/or adaptive antitumor immune response.Mechanisms of suppression include the acquisition of inhibitory ligand expression, and phosphorylation of Stat3, and induction of IL-10 and TGF-β, resulting in a Breg phenotype. Breg suppressive activity may affect diverse cell subtypes, including T effector cells, NK cells, myeloid derived suppressor cells (MDSC) and/or tumor associated macrophages. B cells may also directly promote tumorigenesis through recruitment of inflammatory cells, and upregulation of pro-angiogenic genes and pro-metastatic collagenases.Breg infiltration has now been identified in a variety of solid tumor malignancies including but not limited to ovarian, gastric, non-small cell lung cancer, pancreatic, esophageal, head and neck, and hepatocellular carcinomas. Increasing evidence suggests that recruitment of B cells and acquisition of suppressive activity within the tumor bed may be an important mechanism through which B cells may modulate innate and/or adaptive anti-tumor immunity. B cell depletion in the clinic using anti-CD20 antibodies and/or inhibitors of BTK and/or other signaling pathways, may be a useful strategy for augmenting the anti-tumor immune response.

show abstract

Regulatory B10 cells play a protective role in severe acute pancreatitis

Abstract: Thus, we identified B10 cells as a protective factor for SAP and provided a novel target for SAP treatment.

Cited by 13 publications

References 26 publications

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease

Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing pancreatitis in rats

B cell regulation of the anti-tumor response and role in carcinogenesis

Contact Info

Product

Resources

About