scholarly journals Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease

2017 ◽  
Vol 23 (18) ◽  
pp. 3240 ◽  
Author(s):  
James D Lord ◽  
Donna M Shows
1990 ◽  
Vol 4 (7) ◽  
pp. 303-308 ◽  
Author(s):  
F Hadziselimovic ◽  
LR Emmons ◽  
U Schaub

The occurrence of natural killer cells and large granular lymphocytes (LGL) within the epithelium of colonic mucosa in children with inflammatory bowel disease (IBD) was compared to normal controls. Their numbers and localization within the epithelium from various regions of the colon were analyzed with immunohistochemical techniques using fluorescent, light and electron microscopy. The average number of natural killer cells and LGL in normal controls was 3.0±1.l per mn2. In contrast, there were no natural killer cells in the gut epithelium of children with IBD, irrespective of disease activity, whether the biopsy specimens were obtained from involved or uninvolved inflammatory regions of the gut, or the treatment status of the patients. However, the number of natural killer cells was normal in patients in remission with left-sided colitis. The lack of natural killer cells and LGL in the gut epithelium in children with IBD may be indicative of a possible genetic predisposition. The authors also present a new therapeutic strategy consisting of low dose interferon-alpha-2a that is efficacious in ameliorating ulcerative col iris and Crohn's disease and concomitantly increasing the number of natural killer cells and LGL in the gut.


2021 ◽  
Vol 160 (6) ◽  
pp. S-515-S-516
Author(s):  
Francisco Trelles ◽  
Anabelle Cloutier ◽  
Andrea Herrera-Gayol ◽  
Roberto Rodriguez-Suarez ◽  
Katia Betito

2020 ◽  
Vol 18 (4) ◽  
pp. 402-411
Author(s):  
Chansu Lee ◽  
Sung Noh Hong ◽  
Young-Ho Kim

Background/Aims: The modulation of CD1d-restricted natural killer T (NKT) cells by glycolipids has been considered as a potential therapy against immunologic diseases, including inflammatory bowel disease. A recently identified a glycolipid analog, 7DW8-5, which is derived from α-galactosylceramide (α-GalCer), is as much as 100-fold more active at stimulating both human and mice NKT cells when compared to α-GalCer. We explored the effects of 7DW8-5 in mouse models of acute and chronic colitis.Methods: We investigated the effects of 7DW8-5 on intestinal inflammation by assessing the effects of 7dW8-5 on a murine dextran sulfate sodium (DSS)-induced acute colitis model and a chronic colitis-associated tumor model.Results: The acute DSS-induced colitis model showed a dose-dependent response to 7DW8-5, as mice administered 7DW8-5 showed a significant improvement in DSS-induced colitis based on their disease activity index, histologic analysis, and serum C-reactive protein levels, when compared to mice administered vehicle alone. However, DSS-induced colitis in CD1d-KO mice showed no response to 7DW8-5. A fluorescence-activating cell sorting analysis revealed an increase in NKT cells in colonic tissues of 7DW8-5-treated mice. RNA-seq and real-time quantitative polymerase chain reaction showed a significant increase in the expression of interleukin (IL)-4, IL-13, and interferon-gamma in 7DW8-5-treated mice. In addition, 7DW8-5 treatment reduced colitis-associated tumor development in an azoxymethane/DSS mouse model.Conclusions: 7DW8-5 activates NKT cells through CD1d and provides a protective effect against intestinal inflammation in mice. Therefore, 7DW8-5 may be a promising therapeutic agent for treatment of inflammatory bowel disease.


2007 ◽  
Vol 7 (3) ◽  
pp. 281-286 ◽  
Author(s):  
Y. VAN DE WAL ◽  
A. VAN DER SLUYS VEER ◽  
H. W. VERSPAGET ◽  
T. P. J. MULDER ◽  
G. GRIFFIOEN ◽  
...  

PEDIATRICS ◽  
2010 ◽  
Vol 126 (4) ◽  
pp. e977-e981 ◽  
Author(s):  
M. Deneau ◽  
J. Wallentine ◽  
S. Guthery ◽  
M. O'Gorman ◽  
J. Bohnsack ◽  
...  

Author(s):  
Vanessa Zaiatz Bittencourt ◽  
Fiona Jones ◽  
Miriam Tosetto ◽  
Glen A Doherty ◽  
Elizabeth J Ryan

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.


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