Targeted intestinal ROS scavenging alleviated rheumatoid arthritis by microbial metabolite kynurenic acid mediated Treg/Th17 balance through AhR pathway activation.
7 affiliations
- 1Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
- 2Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, China.
- 3Department of Orthopedics, 923rd Hospital of the People's Liberation Army of China, Nanning, China.
- 4Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing, China.
- 5Senior Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, China.
- 6National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, China.
- 7Department of Orthopedics, Chinese PLA 76th Army Corps Hospital, Xining, China.
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by immune dysregulation, which is often closely related to impaired gut microbiota homeostasis. Excessive reactive oxygen species (ROS) are recognized as critical drivers of microecological immunity disturbance, contributing directly to the inflammatory cascade. However, the underlying mechanism remains unclear. Here, we have used ROS scavengers to alleviate RA progression via inhibiting intestinal ROS and modulating gut microbial kynurenic acid metabolism. Black phosphorus nanosheets (BPNSs), as effective ROS scavengers, significantly ameliorated disease severity in collagen-induced arthritis (CIA) mice by oral administration to eliminate intestinal excess ROS. BPNSs selectively reshaped the gut microbiota and altered its metabolic profile, elevating the relative abundance of the tryptophan-derived metabolite kynurenic acid (KYNA). Mechanistically, elevated KYNA activated the aryl hydrocarbon receptor (AhR) pathway in naïve CD4⁺ T cells, promoting their differentiation into Treg cells through the inhibition of AKT/mTOR signaling pathway. The therapeutic effect of KYNA was further corroborated in CIA mice, where its administration maintained Treg/Th17 balance, attenuated arthritis progression, and enhanced intestinal barrier integrity. These findings elucidate novel gut-immune-bone axis wherein scavenging intestinal ROS drives KYNA mediated AhR-dependent Treg cell differentiation, thereby proposing a promising ROS scavenging-based strategy for RA treatment.
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BibTeX
@article{ling2026targeted,
title = {{Targeted intestinal ROS scavenging alleviated rheumatoid arthritis by microbial metabolite kynurenic acid mediated Treg/Th17 balance through AhR pathway activation.}},
author = {Zhiguo Ling and Tingwen Xiang and Chuan Yang and Dongyang Zhang and Yanghao You and Shiyu Xiao and Langlang Xie and Jiulin Tan and Qijie Dai and Gang Huang and Dong Sun and Fei Luo and Yueqi Chen},
journal = {Gut microbes},
year = {2026},
month = oct,
doi = {10.1080/19490976.2026.2739669},
url = {https://europepmc.org/article/MED/42888947},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Targeted intestinal ROS scavenging alleviated rheumatoid arthritis by microbial metabolite kynurenic acid mediated Treg/Th17 balance through AhR pathway activation.
AU - Zhiguo Ling
AU - Tingwen Xiang
AU - Chuan Yang
AU - Dongyang Zhang
AU - Yanghao You
AU - Shiyu Xiao
AU - Langlang Xie
AU - Jiulin Tan
AU - Qijie Dai
AU - Gang Huang
AU - Dong Sun
AU - Fei Luo
AU - Yueqi Chen
PY - 2026
DA - 2026/10/17
JO - Gut microbes
DO - 10.1080/19490976.2026.2739669
UR - https://europepmc.org/article/MED/42888947
AB - Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by immune dysregulation, which is often closely related to impaired gut microbiota homeostasis. Excessive reactive oxygen species (ROS) are recognized as critical drivers of microecological immunity disturbance, contributing directly to the inflammatory cascade. However, the underlying mechanism remains unclear. Here, we have used ROS scavengers to alleviate RA progression via inhibiting intestinal ROS and modulating gut microbial kynurenic acid metabolism. Black phosphorus nanosheets (BPNSs), as effective ROS scavengers, significantly ameliorated disease severity in collagen-induced arthritis (CIA) mice by oral administration to eliminate intestinal excess ROS. BPNSs selectively reshaped the gut microbiota and altered its metabolic profile, elevating the relative abundance of the tryptophan-derived metabolite kynurenic acid (KYNA). Mechanistically, elevated KYNA activated the aryl hydrocarbon receptor (AhR) pathway in naïve CD4⁺ T cells, promoting their differentiation into Treg cells through the inhibition of AKT/mTOR signaling pathway. The therapeutic effect of KYNA was further corroborated in CIA mice, where its administration maintained Treg/Th17 balance, attenuated arthritis progression, and enhanced intestinal barrier integrity. These findings elucidate novel gut-immune-bone axis wherein scavenging intestinal ROS drives KYNA mediated AhR-dependent Treg cell differentiation, thereby proposing a promising ROS scavenging-based strategy for RA treatment.
SN - 1949-0976
SN - 1949-0984
ER -