Macrophage SELENOP controls neutrophil homeostasis through redox stress regulation in Crohn's disease
5 affiliations
- 1Department of General Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, Jiangsu, China
- 2Department of Gastroenterology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, Jiangsu, China; Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China
- 3Department of Gastroenterology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, Jiangsu, China; Corresponding author.
- 4Department of Gastroenterology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China; Corresponding author.
- 5Department of Gastrointestinal Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, The Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China; Corresponding author.
Abstract
Background: Neutrophil accumulation and oxidative injury are prominent features of Crohn's disease (CD). This study aimed to investigate whether macrophage-derived SELENOP functions as a redox checkpoint in macrophage–neutrophil crosstalk during CD. Methods: Inflamed and non-inflamed colon tissues from CD patients were examined by single-cell RNA sequencing. SELENOP function was assessed in macrophages, macrophage–neutrophil co-cultures and inflammation models. Mechanistic studies included loss- and gain-of-function assays, co-immunoprecipitation, ubiquitination assays, and rescue experiments. In vivo validation was performed using myeloid-specific SELENOP-deficient mice with TNBS-induced colitis and SELENOP-overexpressing IL-10-deficient mice. Results: SELENOP was selectively diminished in colon macrophages from inflamed CD lesions and its reduction was associated with more severe disease activity and postoperative recurrence. Functionally, SELENOP reduction in macrophages acquired a pro-oxidative and hyperinflammatory state through SESN2/NRF2 antioxidant signaling and CAP1. TRIP12 promoted ubiquitin-dependent SELENOP degradation, whereas CREB1 and SMARCA4 cooperatively activated SELENOP transcription. SELENOP-deficient macrophages altered redox and cADPR-associated metabolic signaling, thereby inducing neutrophil oxidative stress, apoptosis and NET formation. Myeloid SELENOP deletion aggravated experimental TNBS-induced colitis, while SELENOP overexpression alleviated IL-10-deficient colitis in a macrophage-dependent manner. Conclusions: Our findings identify macrophage-derived SELENOP as a redox checkpoint that restrains pathogenic macrophage–neutrophil communication in CD. Targeting the macrophage SELENOP may recalibrate oxidative stress-driven colonic inflammation.
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BibTeX
@article{wang2026macrophage,
title = {{Macrophage SELENOP controls neutrophil homeostasis through redox stress regulation in Crohn's disease}},
author = {Honggang Wang and Juan Wang and Wenliang Jiang and Chao Cheng and Shaoqi Cheng and Shuqiang Fu and Yi Zhang and Cuixia Liu and Jing Sun and Jie Zhao},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104377},
url = {https://doi.org/10.1016/j.redox.2026.104377},
note = {CC BY},
}
RIS
TY - JOUR
TI - Macrophage SELENOP controls neutrophil homeostasis through redox stress regulation in Crohn's disease
AU - Honggang Wang
AU - Juan Wang
AU - Wenliang Jiang
AU - Chao Cheng
AU - Shaoqi Cheng
AU - Shuqiang Fu
AU - Yi Zhang
AU - Cuixia Liu
AU - Jing Sun
AU - Jie Zhao
PY - 2026
DA - 2026/10/30
JO - Redox Biology
DO - 10.1016/j.redox.2026.104377
UR - https://doi.org/10.1016/j.redox.2026.104377
AB - Background: Neutrophil accumulation and oxidative injury are prominent features of Crohn's disease (CD). This study aimed to investigate whether macrophage-derived SELENOP functions as a redox checkpoint in macrophage–neutrophil crosstalk during CD. Methods: Inflamed and non-inflamed colon tissues from CD patients were examined by single-cell RNA sequencing. SELENOP function was assessed in macrophages, macrophage–neutrophil co-cultures and inflammation models. Mechanistic studies included loss- and gain-of-function assays, co-immunoprecipitation, ubiquitination assays, and rescue experiments. In vivo validation was performed using myeloid-specific SELENOP-deficient mice with TNBS-induced colitis and SELENOP-overexpressing IL-10-deficient mice. Results: SELENOP was selectively diminished in colon macrophages from inflamed CD lesions and its reduction was associated with more severe disease activity and postoperative recurrence. Functionally, SELENOP reduction in macrophages acquired a pro-oxidative and hyperinflammatory state through SESN2/NRF2 antioxidant signaling and CAP1. TRIP12 promoted ubiquitin-dependent SELENOP degradation, whereas CREB1 and SMARCA4 cooperatively activated SELENOP transcription. SELENOP-deficient macrophages altered redox and cADPR-associated metabolic signaling, thereby inducing neutrophil oxidative stress, apoptosis and NET formation. Myeloid SELENOP deletion aggravated experimental TNBS-induced colitis, while SELENOP overexpression alleviated IL-10-deficient colitis in a macrophage-dependent manner. Conclusions: Our findings identify macrophage-derived SELENOP as a redox checkpoint that restrains pathogenic macrophage–neutrophil communication in CD. Targeting the macrophage SELENOP may recalibrate oxidative stress-driven colonic inflammation.
SN - 2213-2317
ER -