KLF4 and CD55 expression and function depend on each other

• DOI: 10.3389/fimmu.2023.1290684
• Publication Date: 2024-02-09T05:08:09Z
• Authors: Feng-Qi An; Guangjin Zhou; Micah T. Harland; Wasim Hussain; Michael G. Strainic; Mukesh K. Jain; M. Edward Medof
• Keywords: KLF4

The transcription factor Kruppel-like 4 (KLF4) regulates the expression of immunosuppressive and anti-thrombotic proteins. Despite its importance in maintaining homeostasis, signals that control mechanism transactivation remain unclarified. CD55 [aka decay accelerating (DAF)], now known to be a regulator T B cell responses, biases between pro- anti-inflammatory processes by controlling autocrine C3a C5a receptor (C3ar1/C5ar1) signaling cells. similarity CD55’s KLF4’s regulatory effects prompted analyses their functional relationship. In vascular endothelial cells (ECs), upregulation accompanied KLF4 via p-CREB CREB Binding Protein (CBP) mechanism. both ECs macrophages, was essential for downregulation pro-inflammatory/pro-coagulant proteins homeostatic Mechanistic studies showed upregulated CD55. turn enabled recruitment CBP needed transcription. Activation adenylyl cyclase resulting from repression C3ar1/C5ar1 concurrently led KLF4-regulated genes, thereby conferring transactivation. Accordingly, silencing statin-treated HUVEC disabled transfer E-selectin eNOS promoter. Importantly, downregulated expression. It did same untreated transitioning low growth hi contact inhibition. function macrophages thus are linked novel gene Because two co-expressed many types, activity may broadly tied antithrombotic activities.