scholarly journals Opportunities to Target T Cell Trafficking in Pediatric Inflammatory Bowel Disease

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.

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S137-S138
Author(s):  
B Roosenboom ◽  
C Smids ◽  
P Wahab ◽  
M Groenen ◽  
E Van Koolwijk ◽  
...  

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

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.


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