scholarly journals Corrigendum: Blood Immune Cell Composition Associated With Obesity and Drug Repositioning Revealed by Epigenetic and Transcriptomic Conjoint Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Jia-Chen Liu ◽  
Sheng-Hua Liu ◽  
Guang Fu ◽  
Xiao-Rui Qiu ◽  
Run-Dong Jiang ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Jia-Chen Liu ◽  
Sheng-Hua Liu ◽  
Guang Fu ◽  
Xiao-Rui Qiu ◽  
Run-Dong Jiang ◽  
...  

This research was designed to analyze the composition of immune cells in obesity and identify novel and potent drugs for obesity management by epigenetic and transcriptomic conjoint analysis. DNA methylation data set (GSE166611) and mRNA expression microarray (GSE18897) were obtained from the Gene Expression Omnibus database. A total of 72 objects (35 obese samples and 37 controls) were included in the study. Immune cell composition analysis, drug repositioning, and gene set enrichment analysis (GSEA) were performed using CIBERSORT, connectivity map (CMap), and GSEA tools. Besides, we performed a single-cell RNA-seq of the immune cells from whole blood samples obtained from one obese patient and one healthy control. mRNA levels of drug target genes were analyzed by qPCR assay in blood samples from six patients and six healthy controls. Immune cell composition analysis found that CD8 + T cells and NK cells were significantly lower in the obese group. 11 drugs/compounds are considered to possess obesity-control potential, such as atorvastatin. Moreover, the expression of drug targets (STAT3, MCL1, PMAIP1, SOD2, FOX O 3, FOS, FKBP5) in obese patients were higher than those in controls. In conclusion, immune cells are potential therapeutic targets for obesity. Our results also contribute to accelerate research on drug development of obesity.


Author(s):  
Cajsa H. Classon ◽  
Muzhen Li ◽  
Ada Lerma Clavero ◽  
Junjie Ma ◽  
Xiaogang Feng ◽  
...  

AbstractIntestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, implying effects on host immune responses in distal barrier tissues. We herein show that the skin of C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus contain higher numbers of CD4+ T cells compared to the skin of uninfected controls. Accumulated CD4+ T cells were H. polygyrus-specific TH2 cells that skewed the skin CD4+ T cell composition towards a higher TH2/TH1 ratio which persisted after worm expulsion. Accumulation of TH2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4+ T cells in the blood and mesenteric lymph nodes draining the infected intestine and was abolished by FTY720 treatment during infection, indicating gut-to-skin trafficking of cells. Remarkably, skin TH2 accumulation was associated with impaired capacity to initiate IFN-γ recall responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. In conclusion, we show that infection by a strictly intestinal helminth has long-term effects on immune cell composition and local immune responses to unrelated antigens in the skin, revealing a novel process for T cell colonisation and worm-mediated immunosuppression in this organ.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S031-S034
Author(s):  
N Maimon ◽  
S Gerassy-Vainberg ◽  
H Bar-Yosef ◽  
A Alpert ◽  
E Starosvetsky ◽  
...  

Abstract Background Anatomical location and extent of disease are main factors that affect inflammatory bowel disease (IBD) course and prognosis. No explanation is available for segmental intestinal involvement in either Crohn’s disease (CD) or ulcerative colitis (UC), or for selective segmental response to therapy or disease complications. Therefore, studying the cellular composition of different intestinal segments may provide pathophysiological insights into these phenomena. Methods We compared location-specific cell composition and function by Cytometry Time-of-Flight (CyTOF), gene expression and single-cell (sc) RNAseq data obtained from 3 independent cohorts of healthy donors and IBD patients during remission and flare-ups. Using CyTOF data (n = 38 biopsies), we built a high-resolution screening of immune cell behaviour along the intestine. We validated the findings with gene expression data of 370 samples, and expanded screening resolution by computational methodologies. We then tested a specific pathway in scRNAseq data (n = 10 paired biopsies from 5 patients) and validated its significance by cell-specific Significance Analysis of Microarrays (csSAM). Results We found a location along the intestine to be a dominant feature determining immune and non-immune cell composition. We observed that inflammation reduced anatomic segregation beyond cell infiltration, and decreased the ability to cope with oxidative stress. An upregulated IL-6 pathway in T regulatory cells in UC patients was recognised as sigmoid-specific compared with known inflammatory IL-6 roles in macrophages, as seen in the right colon. This observation may be linked to colonic perforations associated with anti-IL-6R treatment. Suppressor of cytokine signalling 3 (SOCS3) may control IL-6 location-specific action. Conclusion Our study displays a unique and comprehensive cell map of IBD in a location-specific context, providing potential explanations to unexplained clinical phenomena. These observations may allow to tailor therapies to affected areas with improved therapeutic index and efficacy.


Author(s):  
Hyun Ah Kim ◽  
Stephanie C. Whittle ◽  
Seyoung Lee ◽  
Hannah X. Chu ◽  
Shenpeng R. Zhang ◽  
...  

2018 ◽  
Vol 19 (S4) ◽  
Author(s):  
Shu-Hwa Chen ◽  
Wen-Yu Kuo ◽  
Sheng-Yao Su ◽  
Wei-Chun Chung ◽  
Jen-Ming Ho ◽  
...  

2017 ◽  
Vol 6 (2) ◽  
pp. e1267095 ◽  
Author(s):  
H. van Meir ◽  
R. A. Nout ◽  
M. J. P. Welters ◽  
N. M. Loof ◽  
M. L. de Kam ◽  
...  

2016 ◽  
Vol 109 (1) ◽  
pp. djw192 ◽  
Author(s):  
Rico D. Bense ◽  
Christos Sotiriou ◽  
Martine J. Piccart-Gebhart ◽  
John B. A. G. Haanen ◽  
Marcel A. T. M. van Vugt ◽  
...  

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