2. Academic Validation
  3. Dexamethasone alleviates pulmonary sarcoidosis by regulating the TGF-β/Smad3 signaling to promote Th17/Treg cell rebalance

Dexamethasone alleviates pulmonary sarcoidosis by regulating the TGF-β/Smad3 signaling to promote Th17/Treg cell rebalance

  • Cell Immunol. 2024 Jan-Feb:395-396:104781. doi: 10.1016/j.cellimm.2023.104781.
Yu Zhang 1,  Xuan Jiang 2,  Qing Wang 3,  Jiayi Wu 3,  Juan Zhou 4
Affiliations

Affiliations

  • 1 Department of Respiratory Medicine, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, China; Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, China.
  • 2 Department of Respiratory Medicine, Wuxi Second People's Hospital, Wuxi, Jiangsu 214000, China.
  • 3 Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, China.
  • 4 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, No. 20, Xisi Road, Nantong, Jiangsu 226000, China. Electronic address: [email protected].
PMID: 38159414 DOI: 10.1016/j.cellimm.2023.104781
Abstract

Pulmonary sarcoidosis is an immune-mediated disorder closely related to Th17/Treg cell imbalance. Dexamethasone has been shown to regulate inflammation and immune responses in sarcoidosis patients. However, the underlying mechanisms of dexamethasone regulating Th17/Treg balance in sarcoidosis remain elusive. Herein, we elucidated the function role of TGF-β/SMAD3 signaling in pulmonary sarcoidosis development and explored the underlying mechanism of dexamethasone in treating pulmonary sarcoidosis. We found that the TGF-β/SMAD3 pathway was inactivated in pulmonary sarcoidosis patients. Propionibacterium acnes (PA) induced mouse model was generated to investigate the function of TGF-β/SMAD3 signaling in vivo. Data indicated that IL17A inhibition with neutralizing antibody and activation of TGF-β/SMAD3 signaling with SRI-011381 alleviated granuloma formation in the sarcoidosis mouse model. Moreover, we revealed that the Th17/Treg cell ratio was increased with PA treatment in mouse bronchoalveolar lavage fluid (BALF) and peripheral blood. The concentration of cytokines produced by Th17 cells (IL-17A, IL-23) was up-regulated in the BALF of PA-treated mice, while those produced by Tregs (IL-10, TGF-β1) presented significant reduction. The treatment of IL-17A neutralizing antibody or SRI-011381 was demonstrated to rescue the PA-induced changes in the concentration of IL-17A, IL-23, IL-10, and TGF-β1. Additionally, we demonstrated that dexamethasone treatment activated the TGF-β/SMAD3 signaling in the lung tissues of pulmonary sarcoidosis mice. Dexamethasone was also revealed to promote the rebalancing of the Th17/Treg ratio and attenuated the granuloma formation in pulmonary sarcoidosis. In conclusion, dexamethasone activates the TGF-β/SMAD3 signaling and induces Th17/Treg rebalance, alleviating pulmonary sarcoidosis, which suggests the potential of dexamethasone in treating pulmonary sarcoidosis.

Keywords

Dexamethasone; Immune cells; Pulmonary sarcoidosis; TGF-β/Smad3 signaling; Th17/Treg balance.

Figures
Products