2. Academic Validation
  3. Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes

Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes

  • Cell Death Dis. 2024 Sep 2;15(9):640. doi: 10.1038/s41419-024-07024-7.
Qi Ni # 1,  Le Zhen # 1,  Zhu Zeng # 1,  Jingwen Yang 1,  Yukai Wang 1,  Huanke Xu 1,  Qixiang Zhang 1,  Yongcheng Zhu 2,  Yu Tao 3,  Jing Wang 4,  Qing Liu 4,  Kezheng Yi 4,  Yang Chen 4,  Qian Chen 1,  Guangji Wang 5,  Fang Zhou 6,  Yunlong Shan 7
Affiliations

Affiliations

  • 1 Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  • 2 Genetic Skin Disease Center, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
  • 3 Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Jiangsu Renocell Biotech Co. Ltd., Nanjing, China.
  • 5 Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. guangjiwang@hotmail.com.
  • 6 Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. zf1113@163.com.
  • 7 Key Laboratory of Drug Metabolism and Pharmacokinetics, Haihe Laboratory of Cell Ecosystem, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. immunometabolism@163.com.
  • # Contributed equally.
PMID: 39251573 DOI: 10.1038/s41419-024-07024-7
Abstract

Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the Aryl Hydrocarbon Receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

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