Details

Autor(en) / Beteiligte

• Mo, Qian
• Bolideei, Mansoor
• Rong, Shan-Jie
• Luo, Jia-Hui
• Yang, Chun-Liang
• Lu, Wan-Ying
• Chen, Qi-Jie
• Zhao, Jia-Wei
• Wang, Fa-Xi
• Wang, Ting
• Li, Yang
• Luo, Xi
• Zhang, Shu
• Xiong, Fei
• Yu, Qi-Lin
• Zhang, Zi-Yun
• Liu, Shi-Wei
• Sun, Fei
• Dong, Ling-Li
• Wang, Cong-Yi

Titel

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis

Ist Teil von

• iScience, 2024-06, Vol.27 (6), p.109798, Article 109798

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings. [Display omitted] •High-salt (HS) intake positively correlates with RA severity•HS exacerbates Th17/Treg imbalance via PDPK1-SGK1-FoxO1 signaling•GSK rectifies HS-induced glycolytic reprogramming and Th17/Treg imbalance•GSK mitigates HS-exacerbated RA progression Pharmacology; Natural sciences; Biological sciences; Physiology; Immunology