Mesenchymal stromal cells restrain the Th17 cell response via L-amino-acid oxidase within lymph nodes
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.
Authors
- Qi Ni (ORCID: https://orcid.org/0000-0002-0603-7053)
- Fang Zhou (ORCID: https://orcid.org/0000-0002-8271-4116)
- Guangji Wang (ORCID: https://orcid.org/0000-0002-0777-3896)
- Yukai Wang (ORCID: https://orcid.org/0009-0004-0923-8071)
- Tao Yu (ORCID: https://orcid.org/0000-0003-2030-7870)
- Yunlong Shan (ORCID: https://orcid.org/0000-0002-6954-364X)
- Jingwen Yang (ORCID: https://orcid.org/0000-0002-9195-308X)
- Yang Chen (ORCID: https://orcid.org/0000-0003-0108-8342)
- Le Zhen (ORCID: https://orcid.org/0000-0002-1854-0764)
- Huanke Xu
- Qian Chen (ORCID: https://orcid.org/0000-0002-8566-4847)
- Qixiang Zhang (ORCID: https://orcid.org/0000-0002-6657-5101)
- Yongcheng Zhu
- Zhu Zeng (ORCID: https://orcid.org/0000-0002-1082-3479)
- K. Yi
- Jing Wang (ORCID: https://orcid.org/0000-0002-3793-3264)
- Qing Liu (ORCID: https://orcid.org/0009-0008-9320-450X)
Institutions
- Nanjing University of Chinese Medicine (CN)
- China Pharmaceutical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese Academy of Medical Sciences Dermatology Hospital (CN)
- Jiangsu Province Hospital (CN)
- Viva Biotech (China) (CN)
- State Key Laboratory of Natural Medicine
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1038/s41419-024-07024-7
- Citations
- 5
- Primary Topic
- Mesenchymal stem cell research
- Type
- article
- Field-Weighted Citation Impact
- 2.19
Funders
- National Natural Science Foundation of China
- China Pharmaceutical University
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- State Key Laboratory of Natural Medicines
- Fundamental Research Funds for the Central Universities
- Foundation Research Project of Jiangsu Province