Title:ALKBH5 Expression could Affect the Function of T Cells in Systemic Lupus Erythematosus
Patients: A Case-control Study
Volume: 28
Issue: 27
Author(s): Li-Jun Deng, Xin-Yu Fang, Jun Wu, Qing-Ru Li, Yan-Mei Mao, Rui-Xue Leng, Yin-Guang Fan*Dong-Qing Ye*
Affiliation:
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- Anhui Province Laboratory of Inflammation and Immune-mediated Diseases, Anhui Medical University, Hefei, Anhui, 230032,
China
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, 230032, China
- Anhui Province Laboratory of Inflammation and Immune-mediated Diseases, Anhui Medical University, Hefei, Anhui, 230032,
China
Keywords:
N6-methyladenosine, ALKBH5, peripheral blood mononuclear cells, T cells, systemic lupus erythematosus, case-control study.
Abstract:
Background: N6-methyladenosine (m6A) modification is widespread in eukaryotic mRNA, regulated
by m6A demethylase, AlkB homolog 5 (ALKBH5). However, the role of m6A in systemic lupus erythematosus
(SLE) is still obscure. We explored ALKBH5 expression in SLE patients and its effects on T cells.
Methods: 100 SLE patients and 110 healthy controls were recruited to investigate the expression of ALKBH5
in peripheral blood mononuclear cells (PBMCs). An additional 32 SLE patients and 32 health controls were enrolled
to explore the expression of ALKBH5 in T cells. Then we explored the function of ALKBH5 in T cells
by lentivirus.
Results: The expressions of ALKBH5 were downregulated in both PBMCs and T cells in SLE patients (all
P<0.05). In PBMCs: ALKBH5 mRNA levels were associated with a complement C4 level in plasma (P<0.05).
In T cells: ALKBH5 mRNA levels were downregulated in SLE patients with low complement levels, high antidsDNA,
anti-Sm, anti-RNP, and proteinuria compared with those without, respectively (all P<0.05); ALKBH5
mRNA levels were negatively related with SLE disease activity index score, erythrocyte sedimentation rate,
and anti-dsDNA levels (all P<0.05), and positively correlated with complement C3 and C4 level (all P<0.05).
Functionally, the overexpression of ALKBH5 promoted apoptosis and inhibited the proliferation of T cells (all
P<0.05).
Conclusion: ALKBH5 expression is downregulated in SLE patients and could affect the apoptosis and proliferation
of T cells, but the exact mechanism still needs to be further explored.
