ALKBH5 Expression could Affect the Function of T Cells in Systemic Lupus Erythematosus Patients: A 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 complement C4 level in plasma (P<0.05). In T cells: ALKBH5 mRNA levels were downregulated in SLE patients with low complement levels, high anti-dsDNA, 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: 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.

m6A mRNA methylation-mediated MAPK signaling modulates the nasal mucosa inflammatory response in allergic rhinitis

“…We determined that the mRNA and protein levels of ALKBH5 were higher in the nasal mucosa of AR mice compared with those in control mice ( Figure 6 ). ALKBH5, an important modifier of m6A methylation, has been reported in other immune diseases ( 75 – 77 ). For example, ALKBH5 is highly expressed in lung adenocarcinoma cells under intermittent hypoxia, and knockdown of ALKBH5 inhibits the proliferation and invasion of lung adenocarcinoma cells by reducing the m6A level of Foxm1 ( 78 ).…”

M6A methylation modification in autoimmune diseases, a promising treatment strategy based on epigenetics

“…Overexpression of ALKBH5 promoted apoptosis and inhibits T cell proliferation, thus affecting the disease activity of SLE. However, ALKBH5 is underexpressed in the PBMCs and T cells of SLE patients [ 66 ].…”

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“…We determined that the mRNA and protein levels of ALKBH5 were higher in the nasal mucosa of AR mice compared with those in control mice (Figure 6). ALKBH5, an important modifier of m6A methylation, has been reported in other immune diseases (75)(76)(77). For example, ALKBH5 is highly expressed in lung adenocarcinoma cells under intermittent hypoxia, and knockdown of ALKBH5 inhibits the proliferation and invasion of lung adenocarcinoma cells by reducing the m6A level of Foxm1 (78).…”