scholarly journals P088 Mucosal CD103+ CD4+ and CD103+CD8+ T-cell subsets in the gut of inflammatory bowel disease patients at diagnosis and during follow-up

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S137-S138
Author(s):  
B Roosenboom ◽  
C Smids ◽  
P Wahab ◽  
M Groenen ◽  
E Van Koolwijk ◽  
...  
2019 ◽  
Vol 25 (9) ◽  
pp. 1497-1509 ◽  
Author(s):  
Britt Roosenboom ◽  
Peter J Wahab ◽  
Carolijn Smids ◽  
Marcel J M Groenen ◽  
Elly van Koolwijk ◽  
...  

Abstract Background The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with β7 (Etrolizumab, anti-β7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103+T-cell subsets, both CD4+ and CD8+, in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. Methods Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103+ T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. Results In total, 75 Crohn’s disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103+T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103+CD4+ in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103+CD8+ compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103-CD4+ T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103+ and CD103-T-cell subsets were comparable with healthy controls. Conclusion At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103+CD4+ and CD103+CD8+T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103-T cells was observed during active inflammation.


2016 ◽  
Vol 22 (7) ◽  
pp. 1596-1608 ◽  
Author(s):  
Michael R. Tom ◽  
Ji Li ◽  
Aito Ueno ◽  
Miriam Fort Gasia ◽  
Ronald Chan ◽  
...  

2019 ◽  
Vol 13 (12) ◽  
pp. 1546-1557 ◽  
Author(s):  
Josefine Schardey ◽  
Anna-Maria Globig ◽  
Christine Janssen ◽  
Maike Hofmann ◽  
Philipp Manegold ◽  
...  

Abstract Background and Aims Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because vitamin D [vitD] deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles. Methods T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry. To translate these in vitro findings to the clinic, serum vitD concentrations and clinical outcomes were correlated with T cell phenotype and function in a prospective patient cohort. Results Incubation of peripheral and intestinal T cells with 1,25(OH)2-vitD resulted in strongly reduced frequencies of pro-inflammatory CD4+ and CD8+ T cells producing interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn’s disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CD patients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CD patients resulted in significantly reduced frequencies of CD4+ T cells producing IFNγ, IL-17 and IL-22. Conclusion vitD exerts profound anti-inflammatory effects on peripheral and intestinal CD4+ and CD8+ T cells of IBD patients in vitro and inhibits TH1 and TH17 cytokine production in CD patients in vivo.


2017 ◽  
Vol 188 (1) ◽  
pp. 163-173 ◽  
Author(s):  
C. S. Horjus Talabur Horje ◽  
C. Smids ◽  
J. W. R. Meijer ◽  
M. J. Groenen ◽  
M. K. Rijnders ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Eirini Giannoudaki ◽  
Siobhan Gargan ◽  
Seamus Hussey ◽  
Aideen Long ◽  
Patrick T. Walsh

T cell subsets are considered central orchestrators of inflammation and homeostasis in the intestine and are established targets for the treatment of inflammatory bowel disease. While approaches aimed at the neutralization of T cell effector cytokines have provided significant benefits for pediatric and adult patients, more recent strategies aimed at inhibiting the infiltration of pathogenic T cell subsets have also emerged. In this review, we describe current knowledge surrounding the function of T cell subsets in pediatric inflammatory bowel disease and outline approaches aimed at targeting T cell trafficking to the intestine which may represent a new treatment option for pediatric inflammatory bowel disease.


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