2. Academic Validation
  3. MIF promotes Th17 cell differentiation in rheumatoid arthritis through ATF6 signal pathway

MIF promotes Th17 cell differentiation in rheumatoid arthritis through ATF6 signal pathway

  • Mol Med. 2024 Nov 29;30(1):237. doi: 10.1186/s10020-024-01005-4.
Guozhi Yan 1,  Rongrong Song 2,  Jieyu Zhang 2,  Zhihao Li 1,  Zhantao Lu 1,  Zijian Liu 3,  Xiaokang Zeng 4,  Jie Yao 5 6
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, Guangdong, 528200, China.
  • 2 The Department of Laboratory Medicine, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan, Foshan, Guangdong, China.
  • 3 Department of Laboratory Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 4 Central Laboratory of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, Guangdong, 528200, China. kangki@163.com.
  • 5 Department of Laboratory Medicine, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, Guangdong, 528200, China. lyyaoj@scut.edu.cn.
  • 6 The Department of Laboratory Medicine, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan, Foshan, Guangdong, China. lyyaoj@scut.edu.cn.
PMID: 39614150 DOI: 10.1186/s10020-024-01005-4
Abstract

Rheumatoid arthritis (RA) is a common autoimmune disease that can lead to irreversible joint damage when it occurs, but its pathogenesis has not yet been elucidated. In this study, we explored the roles of macrophage migration inhibitory factor (MIF), endoplasmic reticulum stress (ER stress), and Th17 cells in the pathogenesis of RA. We have preliminarily confirmed that MIF expression in CD4+T cells and the proportion of Th17 cells are increased in active RA patients. We also found that ER stress is activated, initiating ATF6 pathway in the UPR. Additionally, using in vitro stimulation and co-immunoprecipitation experiments, we have confirmed the interaction between MIF and ATF6, which enhances protein expression in ATF6 pathway. Subsequently, in the chromatin immunoprecipitation assay, we observed the enrichment of ATF6 subunit on the promoter sequences of the Th17 cell differentiation genes STAT3 and RORC. Additionally, the differentiation of Th17 cells was disrupted by Ceapin-A7 (ATF6 inhibitor). In summary, our results indicate that MIF enhances ATF6 pathway signaling, which promotes the differentiation of Th17 cells. This could be a potential mechanism underlying the pathogenesis of RA, offering a new direction for the clinical treatment of RA.

Keywords

ATF6; ER stress; MIF; Rheumatoid arthritis; Th17 cell.

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