scholarly journals Potential Role of NK Cells in the Pathogenesis of Inflammatory Bowel Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Praveen K. Yadav ◽  
Chi Chen ◽  
Zhanju Liu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Nk Cells ◽  
Proinflammatory Cytokines ◽  
Bowel Disease ◽  
Cell Activation ◽  
Potential Role ◽  
Nk Cell ◽  
Target Cells ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

NK cells are a major component of the innate immune system and play an important role in the tissue inflammation associated with autoimmune diseases such as inflammatory bowel disease (IBD). NK cells are unique in bearing both stimulatory and inhibitory receptors specific for MHC class I molecules, and their function is regulated by a series of inhibiting or activating signals. The delicate balance between activation and inhibition that decides NK cell final action provides an opportunity for their possible modulatory effect on specific therapeutic settings. Intestinal NK cells are phenotypically distinct from their counterparts in the blood and resemble “helper” NK cells, which have potentially important functions both in promoting antipathogen responses and in the maintenance of intestinal epithelial homeostasis. NK cell activities have been found to be significantly below normal levels in both remissive and active stages of IBD patients. However, some proinflammatory cytokines (e.g., IL-15, IL-21, and IL-23) could potently induce NK cell activation to secret high levels of proinflammatory cytokines (e.g., IFN-γ and TNF) and promote the cytolytic activities against the target cells. This paper provides the characteristics of intestinal NK cells and their potential role in the pathogenesis of IBD.

scholarly journals Dysregulation of metabolic pathways in circulating natural killer cells isolated from inflammatory bowel disease patients

2021 ◽  
Author(s):  
Vanessa Zaiatz Bittencourt ◽  
Fiona Jones ◽  
Miriam Tosetto ◽  
Glen A Doherty ◽  
Elizabeth J Ryan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Bowel Disease ◽  
Metabolic Profile ◽  
Nk Cell ◽  
Intracellular Cytokines ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Risk Of Cancer

Abstract Background and aims Inflammatory Bowel Disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic conditions characterized by severe dysregulation of innate and adaptive immunity resulting in the destruction of the intestinal mucosa. Natural Killer (NK) cells play a pivotal role in the dynamic interaction between the innate and adaptive immune response. There is an increasing appreciation for the key role immunometabolism plays in the regulation of NK cell function, yet little remains known about the metabolic profile, cytokine secretion and killing capacity of human NK cells during active IBD. Methods PBMC were isolated from peripheral blood of patients with moderate to severely active IBD and healthy controls. NK cells were stained with a combination of cell surface receptors, intracellular cytokines, proteins and analyzed by flow cytometry. For measurements of NK cell cytotoxicity, the calcein-AM release assay was performed. Metabolic profile was analyzed by extracellular flux analyzer. Results NK cells from IBD patients produce large quantities of pro-inflammatory cytokines, IL-17A and TNF-α ex vivo but have limited killing capability. Furthermore, patient NK cells have reduced mitochondrial mass and oxidative phosphorylation. mTORC1, an important cell and metabolic regulator, demonstrated limited activity in both freshly isolated cells and cytokine stimulated cells. Conclusions Our results demonstrate that circulating NK cells of IBD patients have an unbalanced metabolic profile, with faulty mitochondria and reduced capacity to kill. These aberrations in NK cell metabolism may contribute to defective killing and thus the secondary infections and increased risk of cancer observed in IBD patients.

scholarly journals Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease

2008 ◽  
Vol 105 (46) ◽  
pp. 17931-17936 ◽  
Author(s):  
Danyvid Olivares-Villagómez ◽  
Yanice V. Mendez-Fernandez ◽  
Vrajesh V. Parekh ◽  
Saif Lalani ◽  
Tiffaney L. Vincent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Genetic Model ◽  
Critical Role ◽  
Intraepithelial Lymphocytes ◽  
Lymphocyte Function ◽  
Intestinal Epithelial ◽  
Inflammatory Bowel

Intestinal intraepithelial lymphocytes (IEL) bear a partially activated phenotype that permits them to rapidly respond to antigenic insults. However, this phenotype also implies that IEL must be highly controlled to prevent misdirected immune reactions. It has been suggested that IEL are regulated through the interaction of the CD8αα homodimer with the thymus leukemia (TL) antigen expressed by intestinal epithelial cells. We have generated and characterized mice genetically-deficient in TL expression. Our findings show that TL expression has a critical role in maintaining IEL effector functions. Also, TL deficiency accelerated colitis in a genetic model of inflammatory bowel disease. These findings reveal an important regulatory role of TL in controlling IEL function and intestinal inflammation.

Reactive Oxygen Species Scavenging Hollow MnO2 Nanozymes as Carriers Deliver Budesonide for the Synergistic Inflammatory Bowel Disease Therapy

2021 ◽  
Author(s):  
Huiqiang Qiu ◽  
Hengtai Gong ◽  
Yuheng Bao ◽  
Hong Jiang ◽  
Weijun Tong
Keyword(s):  
Reactive Oxygen Species ◽  
Inflammatory Bowel Disease ◽  
Proinflammatory Cytokines ◽  
Bowel Disease ◽  
Active Drug ◽  
Drug Carrier ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Disease Therapy ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is related to excessive reactive oxygen species (ROS) and high expression of proinflammatory cytokines. An enzymatically active drug carrier, which can simultaneously scavenge excessive ROS and...

scholarly journals MiR-155-Mediated Deregulation of GPER1 Plays an Important Role in the Gender Differences Related to Inflammatory Bowel Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaojuan Shao ◽  
Jintao Li ◽  
Fumin Xu ◽  
Dongfeng Chen ◽  
Kaijun Liu
Keyword(s):  
Gender Differences ◽  
Inflammatory Bowel Disease ◽  
Estrogen Receptor ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Bowel Disease ◽  
Clinical Characteristics ◽  
Intestinal Flora ◽  
Inflammatory Bowel ◽  
Proinflammatory Activity

Aim. The incidence and clinical manifestations of inflammatory bowel disease (IBD) are thought to have gender differences, which suggests that the estrogen signaling pathway and intestinal flora may play key roles in the pathogenesis of IBD. In IBD, microRNA-155 (miR-155) is upregulated and regulates G protein coupled estrogen receptor (GPER1), which affects the intestinal flora. The objective of this study was to investigate the role of the estrogen receptors and miR-155 in the pathogenesis of IBD. Methods. From July 2018 to July 2019, in the Department of Gastroenterology at Daping Hospital, Army Military Medical University, a total of 50 patients with IBD were included in this study, and 24 healthy examinees were randomly selected as the control group. Colonoscopies were performed, and clinical characteristics and blood samples were collected from all of the subjects. The serum cytokine levels in the patients with IBD and the health donors were detected by ELISA, and the estrogen receptor level measurements for all of the participants were assessed by immunohistochemistry (IHC) and quantitative real-time PCR (qPCR). The miR-155 levels were detected by qPCR in all of the participants, and miR-155−/− mice were used to investigate the mechanism of miR-155 in the pathogenesis of IBD. Results. The clinical characteristics and medications were different for the IBD patients when gender was considered. The male patients produced more proinflammatory cytokines, and while GPER1 expression was downregulated, miR-155 was upregulated in the patients with IBD. MiR-155 showed proinflammatory activity, while GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The miR-155−/− mice showed improvements in weight loss, survival, rectal bleeding, colon length, and histopathological changes compared with the wild-type mice. Furthermore, the male miR-155−/− mice showed increased inflammation compared to the female miR-155−/− mice in the above aspects. Conclusion. This study presents evidence indicating that miR-155 plays a key role in the pathogenesis of IBD for the different genders. MiR-155 was upregulated and showed proinflammatory activity, whereas GPER1 showed an anti-inflammatory response during the pathogenesis of IBD. The results demonstrated that more proinflammatory cytokines and reduced GPER1 levels were observed in the male IBD patients. Thus, miR-155 was involved in the regulation of GPER1 and induced gender differences in IBD patients. MiR-155 may be a potential marker for IBD-targeted therapy.

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