Genes, Microbes, and T Cells — New Therapeutic Targets in Crohn's Disease

2002 ◽  
Vol 346 (8) ◽  
pp. 614-616 ◽  
Author(s):  
Charles O. Elson
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

IL-1 and CD40/CD40L platelet complex: elements of induction of Crohn’s disease and new therapeutic targets

2021 ◽  
Author(s):  
Doha Anka Idrissi ◽  
Nezha Senhaji ◽  
Asmae Aouiss ◽  
Loubna Khalki ◽  
Youssef Tijani ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

scholarly journals TNFSF15 transcripts from risk haplotype for Crohn's disease are overexpressed in stimulated T cells

2009 ◽  
Vol 18 (6) ◽  
pp. 1089-1098 ◽  
Author(s):  
Yoichi Kakuta ◽  
Nobuo Ueki ◽  
Yoshitaka Kinouchi ◽  
Kenichi Negoro ◽  
Katsuya Endo ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Risk Haplotype

scholarly journals CD4+ Tissue-resident Memory T Cells Expand and Are a Major Source of Mucosal Tumour Necrosis Factor α in Active Crohn’s Disease

2019 ◽  
Vol 13 (7) ◽  
pp. 905-915 ◽  
Author(s):  
Shrinivas Bishu ◽  
Mohammed El Zaatari ◽  
Atsushi Hayashi ◽  
Guoqing Hou ◽  
Nicole Bowers ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Ex Vivo ◽  
Factor Α ◽  
And Control ◽  
Necrosis Factor

Abstract Background and Aims Tumour necrosis factor [TNF]α- and IL-17A-producing T cells are implicated in Crohn’s disease [CD]. Tissue-resident memory T [TRM] cells are tissue-restricted T cells that are regulated by PR zinc finger domain 1 [PRDM1], which has been implicated in pathogenic Th17 cell responses. TRM cells provide host defence but their role in CD is unknown. We thus examined CD4+ TRM cells in CD. Methods Colon samples were prospectively collected at endoscopy or surgery in CD and control subjects. Flow cytometry and ex vivo assays were performed to characterise CD4+ TRM cells. Results CD4+ TRM cells are the most abundant memory T cell population and are the major T cell source of mucosal TNFα in CD. CD4+ TRM cells are expanded in CD and more avidly produce IL-17A and TNFα relative to control cells. There was a unique population of TNFα+IL-17A+ CD4+ TRM cells in CD which are largely absent in controls. PRDM1 was highly expressed by CD4+ TRM cells but not by other effector T cells. Suppression of PRDM1 was associated with impaired induction of IL17A and TNFA by CD4+ TRM cells Conclusions CD4+ TRM cells are expanded in CD and are a major source of TNFα, suggesting that they are important in CD. PRDM1 is expressed by TRM cells and may regulate their function. Collectively, this argues for prospective studies tracking CD4+ TRM cells over the disease course.

scholarly journals Regulatory T-cell therapy in Crohn’s disease: challenges and advances

Gut ◽  
2020 ◽  
Vol 69 (5) ◽  
pp. 942-952 ◽  
Author(s):  
Jennie N Clough ◽  
Omer S Omer ◽  
Scott Tasker ◽  
Graham M Lord ◽  
Peter M Irving
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Regulatory T Cells ◽  
Cell Therapy ◽  
Regulatory T Cell ◽  
Critical Role ◽  
Significant Proportion ◽  
T Cell Therapy

The prevalence of IBD is rising in the Western world. Despite an increasing repertoire of therapeutic targets, a significant proportion of patients suffer chronic morbidity. Studies in mice and humans have highlighted the critical role of regulatory T cells in immune homeostasis, with defects in number and suppressive function of regulatory T cells seen in patients with Crohn’s disease. We review the function of regulatory T cells and the pathways by which they exert immune tolerance in the intestinal mucosa. We explore the principles and challenges of manufacturing a cell therapy, and discuss clinical trial evidence to date for their safety and efficacy in human disease, with particular focus on the development of a regulatory T-cell therapy for Crohn’s disease.

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