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Downregulating LKB1 in bone marrow mesenchymal stem cells could inhibit CD4+ T cell proliferation via the PD-1/PD-L1 signaling pathway

Year: 2024

Type: article

Abstract: Our previous research has shown that LKB1 in amniotic mesenchymal stem cells (MSCs) serves as a vital regulator of regulatory T cell differentiation and T cell proliferation, which may have a similar role in bone marrow MSCs (BMMSCs). Therefore, we investigated the role of LKB1 in BMMSCs for regulating CD4 + T cell proliferation in the bone micro-environment of AML. RT-PCR was used to assessed LKB1 expression in BMMSCs derived from AML patients and healthy controls. Subsequently, LKB1 was knocked down in the BMMSCs line HS-5 (HS-5-LKB1 KD ). Co-cultures in vitro were established to analyze the effect of HS-5-LKB1 KD on CD4 + T cell. Flow cytometry was employed to measure PD-L1 and CD4 + T cell proliferation levels. Western blot was utilized to detect related proteins. The expression of LKB1 in BMMSCs derived from AML patients was decreased. Knockdown of LKB1 in HS-5 resulted in upregulation of PD-L1 expression. Co-culture of peripheral blood CD4 + T cell with HS-5-LKB1 KD exhibited reduced CD4 + T cell proliferation compared to co-culture with HS-5-LKB1 con . Furthermore, blocking PD-L1 in the co-culture conditions could restore the reduced CD4 + T cell proliferation. Additionally, it was found that upregulation of the Wnt signaling pathway-related proteins following LKB1 knockdown in HS-5, indicating that downregulating LKB1 could promote PD-L1 expression through activation of the Wnt signaling pathway. The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4 + T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.

Source: Immunobiology

DOI: 10.1016/j.imbio.2024.152856