Evaluating IL-21 as a Potential Therapeutic Target in Crohn’s Disease
Joint Authors
Kvist, Peter H.
Tornehave, Ditte
Søndergaard, Henrik
Sondergaard, Bodil-Cecilie
Hansen, Lene
Hermit, Mette Brunsgaard
Holgersen, Kristine
Vergo, Sandra
Frederiksen, Klaus Stensgaard
Haase, Claus
Lundsgaard, Dorthe
Lindebo Holm, Thomas
Source
Gastroenterology Research and Practice
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-22, 22 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-10
Country of Publication
Egypt
No. of Pages
22
Main Subjects
Abstract EN
Background and Aim.
Interleukin-21 (IL-21) is primarily a T cell-derived cytokine; it is upregulated in patients with Crohn’s Disease (CD) and could be a potential new therapeutic target in CD.
Methods.
In human material, IL-21 and IL-21R expression was investigated by in situ hybridization (ISH) and immunohistochemistry (IHC) in noninflammatory bowel disease (non-IBD) controls and patients with CD.
The pathologic role of IL-21 was examined in murine models of T cell-dependent and T cell-independent colitis, either with a neutralizing monoclonal antibody against IL-21 or with the transfer of CD4+CD45RBhighIL-21R−/− T cells.
Colonic pathology was examined by endoscopy, histopathology, IHC, ELISA, and Luminex.
Results.
In the human intestine, IL-21 and IL-21R mRNA and protein-expressing cells were observed in the mucosa, in lymphoid aggregates of submucosa in non-IBD controls, and in lymphoid aggregates of muscularis externa in patients with CD.
IL-21 expression was most abundant in germinal centers (GCs) of the lymphoid aggregates, and IL-21R expression assessed semiquantitatively, was significantly higher in patients with CD compared to non-IBD controls.
Following prophylactic and interventive anti-IL-21 mAb treatment in the adoptive transfer (AdTr) model, clinical and pathological parameters were significantly reduced.
The most persistent finding was a reduction in colonic infiltrating neutrophils.
As well, Rag2−/− mice receiving CD4+CD45RBhighIL-21R−/− T cells developed less severe colitis compared to Rag2−/− mice receiving CD4+CD45RBhighIL-21R+/+ T cells.
No effect of reduced IL-21 signalling was observed in T cell-independent colitis.
Conclusion.
Our study shows that patients with CD have significant expression of IL-21 and IL-21R in the gut.
As well, we show that neutralization of IL-21 in experimental T cell-driven colitis is associated with a reduction in clinical and pathological findings.
This amelioration seems to be associated with a reduction in colon-infiltrating neutrophils.
American Psychological Association (APA)
Lindebo Holm, Thomas& Tornehave, Ditte& Søndergaard, Henrik& Kvist, Peter H.& Sondergaard, Bodil-Cecilie& Hansen, Lene…[et al.]. 2018. Evaluating IL-21 as a Potential Therapeutic Target in Crohn’s Disease. Gastroenterology Research and Practice،Vol. 2018, no. 2018, pp.1-22.
https://search.emarefa.net/detail/BIM-1165181
Modern Language Association (MLA)
Lindebo Holm, Thomas…[et al.]. Evaluating IL-21 as a Potential Therapeutic Target in Crohn’s Disease. Gastroenterology Research and Practice No. 2018 (2018), pp.1-22.
https://search.emarefa.net/detail/BIM-1165181
American Medical Association (AMA)
Lindebo Holm, Thomas& Tornehave, Ditte& Søndergaard, Henrik& Kvist, Peter H.& Sondergaard, Bodil-Cecilie& Hansen, Lene…[et al.]. Evaluating IL-21 as a Potential Therapeutic Target in Crohn’s Disease. Gastroenterology Research and Practice. 2018. Vol. 2018, no. 2018, pp.1-22.
https://search.emarefa.net/detail/BIM-1165181
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1165181