Full Papers
WTAP regulates PTEN through m6A methylation to modulate the inflammatory response in CD4+ T cells from patients with ankylosing spondylitis
Z. Li1, H. Zhao2, L. Cheng3, R. Li4, X. Yu5, Y. Ren6, Y. Zhao7, H. Wu8, L. Xu9, G. Li10, M. Gao11, S. Xu12, Z. Shuai13, F. Pan14
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui; and Anhui Public Health Clinical Center, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Clinical Medicine, Clinical College of Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China.
- Department of Rheumatism and Immunity, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
- Department of Rheumatism and Immunity, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui; and The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China. famingpan@ahmu.edu.cn
CER20282
Full Papers
PMID: 43001851 [PubMed]
Received: 30/06/2026
Accepted : 30/09/2026
In Press: 05/11/2026
Abstract
OBJECTIVES:
This study aimed to investigate how Wilms’ tumour 1-related protein (WTAP)-mediated m6A methylation regulates PTEN and thereby influences the inflammatory response in ankylosing spondylitis (AS) through a combination of a case-control study and cellular experiments.
METHODS:
The study enrolled 45 AS patients and 45 age- and gender-matched healthy controls. Peripheral venous blood (10 mL) was drawn from each participant, and CD4+ T lymphocytes were isolated using a human positive selection kit. mRNA expression levels of WTAP and PTEN were measured by quantitative real-time PCR (qRT-PCR). Plasma was separated by centrifugation and subjected to enzyme-linked immunosorbent assay (ELISA) to quantify inflammatory cytokine concentrations. A WTAP-knockdown model was established in human Jurkat T cells using small interfering RNA (siRNA), followed by analysis of downstream gene transcription and protein expression via qRT-PCR and Western blotting, respectively. After WTAP knockdown, the m6A modification level of PTEN mRNA in Jurkat cells was determined by MeRIP-qPCR.
RESULTS:
Results showed that WTAP and PTEN expression levels in CD4+ T lymphocytes were significantly downregulated in AS patients compared to healthy controls, and both were inversely correlated with TNF-α levels. Moreover, WTAP knockdown in Jurkat T cells led to a marked decrease in both PTEN expression and its m6A modification, which coincided with a significant increase in TNF-α expression.
CONCLUSIONS:
In conclusion, WTAP downregulation promotes AS inflammation by decreasing PTEN expression through an m6A-dependent mechanism.
