Single-cell RNA sequencing reveals Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131-TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.
10.1016/j.apsb.2025.05.013
- Author:
Yuquan TAO
1
;
Yinuo MA
2
;
Limei GU
3
;
Ye ZHANG
1
;
Qinchang ZHANG
1
;
Lisha ZHOU
2
;
Jie PAN
2
;
Meng SHEN
1
;
Xuefei ZHUANG
4
;
Linmei PAN
4
;
Weixing SHEN
1
;
Chengtao YU
1
;
Dan DONG
1
;
Dong ZHANG
1
;
Tingsheng LING
3
;
Yang SUN
2
;
Haibo CHENG
1
Author Information
1. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, the First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.
3. Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
4. Jiangsu Botanical Medicine Refinement Engineering Research Center, Nanjing University of Chinese Medicine, Nanjing 210023, China.
- Publication Type:Journal Article
- Keywords:
CCL22+ dendritic cells;
CD4+ regulatory T cells;
Colorectal tumorigenesis;
Single-cell RNA sequencing;
TMEM131;
TNF signaling pathway;
Traditional Chinese medicine;
Tumor microenvironment
- From:
Acta Pharmaceutica Sinica B
2025;15(7):3545-3560
- CountryChina
- Language:English
-
Abstract:
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc Min/+ mice and clinical patients. There was a marked accumulation of CCL22+ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22+ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22+ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.
