Murine T-Cell Transfer Colitis as a Model for Inflammatory Bowel Disease

2021 ◽  
pp. 349-373
Author(s):  
Patrick Maschmeyer ◽  
Jakob Zimmermann ◽  
Anja Andrea Kühl
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
T Cell Transfer

scholarly journals Carboxylesterase-1 assisted targeting of HDAC inhibitors to mononuclear myeloid cells in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Ahmed M I Elfiky ◽  
Mohammed Ghiboub ◽  
Andrew Y F Li Yim ◽  
Ishtu L Hageman ◽  
Jan Verhoeff ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Bowel Disease ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
Carboxylesterase 1 ◽  
T Cell Transfer

Abstract Background and Aims Histone deacetylase inhibitors (HDACi) exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif (ESM) technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 (CES1). This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease (IBD). Methods CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells and Crohn's disease (CD) colon mucosa by mass cytometry, quantitative PCR and immunofluorescence staining respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in DSS-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promotor. Results CES1 mRNA was highly expressed in human blood CD14 + monocytes, in vitro differentiated and LPS stimulated macrophages and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1 + cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1 high monocytes. In healthy donors peripheral blood, CES1 expression was significantly higher in CD14 ++CD16 - monocytes compared to CD14 +CD16 ++ monocytes. In CD inflamed colon, a higher number of mucosal CD68 + macrophages expressed CES1 compared to non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, whilst having limited potential in ameliorating DSS-induced colitis. Conclusions We demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

Balance of NLRP3-Mediated IL-1β and IL-18 Signaling Regulates Colitis Induction in a T Cell Transfer Model of Inflammatory Bowel Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S615
Author(s):  
Rachel Mak'Anyengo ◽  
Peter Duewell ◽  
Hans Anton Lehr ◽  
Sandra Fischer ◽  
Thomas Clavel ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Transfer Model ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
T Cell Transfer

T-cell transfer and cytokine/TCR gene deletion models in the study of inflammatory bowel disease

Apmis ◽  
1997 ◽  
Vol 105 (7-12) ◽  
pp. 655-662 ◽  
Author(s):  
SØOREN BREGENHOLT ◽  
DICK DELBRO ◽  
MOGENS H. CLAESSON
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Gene Deletion ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
T Cell Transfer

scholarly journals Association between blood flow and inflammatory state in a T-cell transfer model of inflammatory bowel disease in mice

2010 ◽  
Vol 16 (5) ◽  
pp. 776-782 ◽  
Author(s):  
Norman R. Harris ◽  
Patsy R. Carter ◽  
Seungjun Lee ◽  
Megan N. Watts ◽  
Songlin Zhang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Blood Flow ◽  
T Cell ◽  
Bowel Disease ◽  
Transfer Model ◽  
Cell Transfer ◽  
Inflammatory State ◽  
Inflammatory Bowel ◽  
T Cell Transfer

rHuKGF ameliorates symptoms in DSS and CD4+CD45RBHi T cell transfer mouse models of inflammatory bowel disease

2002 ◽  
Vol 282 (4) ◽  
pp. G690-G701 ◽  
Author(s):  
Fergus R. Byrne ◽  
Catherine L. Farrell ◽  
Richard Aranda ◽  
Karen L. Rex ◽  
Sheila Scully ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Body Weight ◽  
T Cell ◽  
Large Intestine ◽  
Bowel Disease ◽  
Body Weight Loss ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
T Cell Transfer

There is an acute need for effective therapy for inflammatory bowel disease (IBD), particularly at the level of repair of the damaged epithelium. We evaluated the efficacy of recombinant human keratinocyte growth factor (rHuKGF) in both the dextran sodium sulfate (DSS) and the CD4+CD45RBHi T cell transfer models of IBD. Disease was induced either by the ad libitum administration to normal mice of 4% DSS in the drinking water or by the injection of 4 × 105 CD4+CD45RBHi T cells into immunodeficient scid/scid mice. rHuKGF was administered by subcutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens during both studies. rHuKGF significantly improved survival and body weight loss in the DSS model in both preventative and therapeutic dosing regimens. It also improved diarrhea, hematochezia, and hematological parameters, as well as large intestine histopathology. In the T cell transfer model, rHuKGF improved body weight loss, diarrhea, and levels of serum amyloid A, as well as large intestine histopathology. In both models of IBD, the colonic levels of intestinal trefoil factor (ITF) were elevated by the disease state and further elevated by treatment with rHuKGF. These data suggest that rHuKGF may prove useful in the clinical management of IBD and its effects are likely mediated by its ability to locally increase the levels of ITF.

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