The final, formatted version of the article will be published soon.
BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1484321
Impairment of regulatory T cell stability in axial spondyloarthritis: role of EZH2 and pSTAT5
Provisionally accepted
majda lyna mebrek
1,2
Tessnime Abaab
1,2
Delphine lemeiter
1,2
Mylène Petit
1,2,3
Roxane Hervé
1,2
Gaelle Clavel
1,2,4
LUCA SEMERANO
1,2,3
Johanna Sigaux
1,2,3
Marie-Christophe Boissier
1,2,3
Jerome Biton
1,2
Natacha BESSIS
1,2*- 1 UMR 1125 INSERM, Bobigny, France
- 2 Sorbonne Paris Nord University, Bobigny, France
- 3 Rheumatology Department, Avicenne Hospital, APHP, Bobigny, France
- 4 Department of Internal Medicine, Fondation Rothschild, PARIS, France
Background and objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease involving the spine, peripheral joints, and entheses. Functional impairment of regulatory T cells (Treg) is linked to inflammatory diseases, but limited data is available regarding Treg involvement in axSpA. Treg stability refers to their ability to maintain their functions and characteristics in pro-inflammatory environments. EZH2 and phosphorylated STAT5 (pSTAT5) play a critical role in maintaining Treg stability. We aimed to characterize Treg stability in axSpA patients. Methods: Peripheral blood mononuclear cells (PBMCs) from axSpA patients, either naïve from targeted therapy or treated by TNF inhibitors (TNFi), and from healthy donors (HD), were freshly isolated. Expression of stability (EZH2, pSTAT5) and suppressive (TNFR2 and CD39) markers by Treg was analyzed by flow cytometry. Results: EZH2 expression by Treg was decreased in axSpA patients as compared to HD (p<0.01). Mechanistic study showed that inhibition of EZH2 attenuated Treg differentiation and suppressive phenotype in vitro. EZH2 was predominantly expressed by highly suppressive TNFR2 + and CD39 + Treg. Additionally, axSpA patients exhibited a reduced frequency of pSTAT5 + Treg compared to HD (p<0.05), and pSTAT5 + Treg frequency increased at 3 months of TNFi treatment compared to baseline (p<0.05). This last result suggested a restoration of Treg stability upon TNFi treatment. Conclusion: By highlighting a deficient expression of EZH2 and pSTAT5 by Treg, we revealed an impaired Treg stability in axSpA. Deciphering the pathways influenced by these molecules is necessary to assess the potential therapeutic benefits of restoring Treg stability in axSpA.
Keywords: regulatory T cells, Spondyloarthritis, TNF inhibitors, EZH2, PSTAT5
Received: 21 Aug 2024; Accepted: 10 Oct 2024.
Copyright: © 2024 mebrek, Abaab, lemeiter, Petit, Hervé, Clavel, SEMERANO, Sigaux, Boissier, Biton and BESSIS. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Natacha BESSIS, UMR 1125 INSERM, Bobigny, France
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.