Fig. 8: Schematic diagram of the proposed mechanism of FPP-induced PMN hyperactivation. | Nature Communications

Fig. 8: Schematic diagram of the proposed mechanism of FPP-induced PMN hyperactivation.

From: TNF inhibitors target a mevalonate metabolite/TRPM2/calcium signaling axis in neutrophils to dampen vasculitis in Behçet’s disease

Fig. 8

Aberrantly elevated metabolite FPP in BD patients promotes PMN hyperactivation via a calcium-TRPM2-dependent pathway, evidenced by the excessive production of proinflammatory cytokines, including TNF, and NETs, which exacerbates vascular endothelium inflammation and damage. In addition, excessive levels of TNF in BD serum triggered the upregulation of TRPM2, which further induced hypersensitivity to FPP in BD-PMN. All these led to significantly increased serum levels of NETs and proinflammatory cytokines, including TNF, ultimately resulting in proinflammatory positive feedback loops in BD. Created in BioRender. Ji, Z. (2024) BioRender.com/d22k224.

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