Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression

Chunhua Huang; Cheng Lyu; Heung Lam Mok; Yiqi Xu; Ka Wing Cheng; Cheng Zhang; Die Hu; Lin Zhu; Chengyuan Lin; Xin Chen; Hor Yue Tan; Zhaoxiang Bian

doi:10.1016/j.jare.2024.04.023

Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression

Chunhua Huang, Cheng Lyu, Heung Lam Mok, Yiqi Xu, Ka Wing Cheng, Cheng Zhang, Die Hu, Lin Zhu, Chengyuan Lin, Xin Chen, Hor Yue Tan^*, Zhaoxiang Bian^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

2 Citations (Scopus)

Abstract

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression.

Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis.

Methods: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1^-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component.

Results: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1^-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation.

Conclusion: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.

Original language	English
Pages (from-to)	1-15
Number of pages	15
Journal	Journal of Advanced Research
DOIs	https://doi.org/10.1016/j.jare.2024.04.023
Publication status	E-pub ahead of print - 26 Apr 2024

User-Defined Keywords

CDD-2103
Chinese herbal formulation
Oxidative phosphorylation
Regulatory T cell
Tolerogenic dendritic cell
Ulcerative colitis

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10.1016/j.jare.2024.04.023

Cite this

Huang, C., Lyu, C., Mok, H. L., Xu, Y., Cheng, K. W., Zhang, C., Hu, D., Zhu, L., Lin, C., Chen, X., Tan, H. Y., & Bian, Z. (2024). Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression. Journal of Advanced Research, 1-15. Advance online publication. https://doi.org/10.1016/j.jare.2024.04.023

@article{5e927eb32a324499b92e67d22a649a7b,

title = "Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression",

abstract = "Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. Methods: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. Results: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. Conclusion: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.",

keywords = "CDD-2103, Chinese herbal formulation, Oxidative phosphorylation, Regulatory T cell, Tolerogenic dendritic cell, Ulcerative colitis",

author = "Chunhua Huang and Cheng Lyu and Mok, {Heung Lam} and Yiqi Xu and Cheng, {Ka Wing} and Cheng Zhang and Die Hu and Lin Zhu and Chengyuan Lin and Xin Chen and Tan, {Hor Yue} and Zhaoxiang Bian",

note = "The study was financially supported by the Health@InnoHK Initiative Fund of the Hong Kong Special Administrative Region Government (ITC RC/IHK/4/7), Key-Area Research and Development Program of Guangdong Province (2020B1111110003), Health and Medical Research Fund (19200701). We express our appreciation to Mr. Hilman Chan, Ms. Ping Yao and Mr. Eugene Chan for their technical support. Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2024",

month = apr,

day = "26",

doi = "10.1016/j.jare.2024.04.023",

language = "English",

pages = "1--15",

journal = "Journal of Advanced Research",

issn = "2090-1232",

publisher = "Cairo University",

}

TY - JOUR

T1 - Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression

AU - Huang, Chunhua

AU - Lyu, Cheng

AU - Mok, Heung Lam

AU - Xu, Yiqi

AU - Cheng, Ka Wing

AU - Zhang, Cheng

AU - Hu, Die

AU - Zhu, Lin

AU - Lin, Chengyuan

AU - Chen, Xin

AU - Tan, Hor Yue

AU - Bian, Zhaoxiang

N1 - The study was financially supported by the Health@InnoHK Initiative Fund of the Hong Kong Special Administrative Region Government (ITC RC/IHK/4/7), Key-Area Research and Development Program of Guangdong Province (2020B1111110003), Health and Medical Research Fund (19200701). We express our appreciation to Mr. Hilman Chan, Ms. Ping Yao and Mr. Eugene Chan for their technical support. Publisher Copyright: © 2023 The Authors.

PY - 2024/4/26

Y1 - 2024/4/26

N2 - Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. Methods: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. Results: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. Conclusion: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.

AB - Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. Objectives: This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. Methods: Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1-/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. Results: CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1-/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. Conclusion: Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.

KW - CDD-2103

KW - Chinese herbal formulation

KW - Oxidative phosphorylation

KW - Regulatory T cell

KW - Tolerogenic dendritic cell

KW - Ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=85192067899&partnerID=8YFLogxK

U2 - 10.1016/j.jare.2024.04.023

DO - 10.1016/j.jare.2024.04.023

M3 - Journal article

AN - SCOPUS:85192067899

SN - 2090-1232

SP - 1

EP - 15

JO - Journal of Advanced Research

JF - Journal of Advanced Research

ER -

Tolerogenic dendritic cell-mediated regulatory T cell differentiation by Chinese herbal formulation attenuates colitis progression

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