Targeting JAK/STAT Signaling Attenuates Postoperative Recurrence in an HLA-B27 Transgenic Rat Model of Crohn’s Disease
5 affiliations
- 1U1286 INFINITE (Institute for Translational Research in Inflammation), Inserm, CHU Lille, Université de Lille, 59000 Lille, France
- 2Department of Hepato-Gastroenterology, CHU Lille, 59000 Lille, France
- 3Department of Digestive Surgery and Transplantation, CHU Lille, 59000 Lille, France
- 4Department of Rheumatology, FHU PRECISE, CHU Lille, Université de Lille, 59000 Lille, France
- 5Intestinal Biotech Development, 59045 Lille, France
Abstract
Postoperative recurrence (POR) remains a common complication following ileocecal resection (ICR) in patients with Crohn’s disease (CD), and no therapy is currently approved. This study aimed to study the benefits of JAK/STAT pathway inhibition in preventing POR using an ICR model in HLA-B27 transgenic (Tg) rats. Twenty-nine Tg rats underwent ICR at 12 weeks of age (W12). TOFA (15 mg/Kg/day) or placebo was administered at W10 as a preventive intervention. Disease extent and severity were assessed by monitoring body weight, stool consistency, performing endoscopy (W15) and evaluating macroscopic and histologic scores (W18). Ileal STATs phosphorylation was assessed by Western blotting and immunohistochemistry, while inflammatory cytokine expression was quantified by qRT-PCR and ELISA. In the placebo-treated Tg group, 57% of rats exhibited mucosal ulcerations in at least 20% of the anastomotic area (macroscopic score ≥2), which correlated with an endoscopic score ≥9. In contrast, only 13% of TOFA-treated Tg rats had a macroscopic score ≥2 and all had endoscopic scores ≤9. TOFA reduced mucosal inflammation and decreased ilealSTAT3 phosphorylation and pro-inflammatory cytokine expression. These findings provide a preclinical rationale for further investigating JAK inhibition as a potential preventive strategy against POR in CD.
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BibTeX
@article{blondeaux2026targeting,
title = {{Targeting JAK/STAT Signaling Attenuates Postoperative Recurrence in an HLA-B27 Transgenic Rat Model of Crohn’s Disease}},
author = {Aurélie Blondeaux and Caroline Valibouze and Marie Titécat and Jean Guillaume Letarouilly and Caroline Dubuquoy and Matthias Danes and Laurent Dubuquoy and Philippe Zerbib and Benoît Foligné and Pierre Desreumaux and Silvia Speca},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219487},
url = {https://www.mdpi.com/1422-0067/27/21/9487},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeting JAK/STAT Signaling Attenuates Postoperative Recurrence in an HLA-B27 Transgenic Rat Model of Crohn’s Disease
AU - Aurélie Blondeaux
AU - Caroline Valibouze
AU - Marie Titécat
AU - Jean Guillaume Letarouilly
AU - Caroline Dubuquoy
AU - Matthias Danes
AU - Laurent Dubuquoy
AU - Philippe Zerbib
AU - Benoît Foligné
AU - Pierre Desreumaux
AU - Silvia Speca
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219487
UR - https://www.mdpi.com/1422-0067/27/21/9487
AB - Postoperative recurrence (POR) remains a common complication following ileocecal resection (ICR) in patients with Crohn’s disease (CD), and no therapy is currently approved. This study aimed to study the benefits of JAK/STAT pathway inhibition in preventing POR using an ICR model in HLA-B27 transgenic (Tg) rats. Twenty-nine Tg rats underwent ICR at 12 weeks of age (W12). TOFA (15 mg/Kg/day) or placebo was administered at W10 as a preventive intervention. Disease extent and severity were assessed by monitoring body weight, stool consistency, performing endoscopy (W15) and evaluating macroscopic and histologic scores (W18). Ileal STATs phosphorylation was assessed by Western blotting and immunohistochemistry, while inflammatory cytokine expression was quantified by qRT-PCR and ELISA. In the placebo-treated Tg group, 57% of rats exhibited mucosal ulcerations in at least 20% of the anastomotic area (macroscopic score ≥2), which correlated with an endoscopic score ≥9. In contrast, only 13% of TOFA-treated Tg rats had a macroscopic score ≥2 and all had endoscopic scores ≤9. TOFA reduced mucosal inflammation and decreased ilealSTAT3 phosphorylation and pro-inflammatory cytokine expression. These findings provide a preclinical rationale for further investigating JAK inhibition as a potential preventive strategy against POR in CD.
SN - 1422-0067
ER -