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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Immunol Rev. 2022 Mar 20;308(1):9–24. doi: 10.1111/imr.13077

Figure 4. Regulation of IFN-β expression and function in trophoblast cells.

Figure 4.

(A) Normal regulation of IFN-β expression and function in trophoblast cells. In normal condition, LPS binds to TLR4 induces IFN-β expression by the phosphorylation of TRIF/TBK1/IRF3, and secreted IFN-β binds to IFNAR and stimulates numerous ISGs expression. These ISGs function as the immune regulators and anti-viral effectors to maintain cellular homeostasis and to inhibit viral replication. Axl and Axl ligand Gas6, inhibits chronic IFN-β expression and its potential toxic effects.

(B) Effect of deletion of Axl on trophoblast function. Lack of Axl expression in trophoblast cells leads to the loss of negative regulation on IFNβ expression, followed by enhanced IFN-β expression and the selective induction of apoptosis related ISGs, such as TRAIL, FAS and CASP1.

LPS, lipopolysaccharides; TLR4, toll like receptor 4; TRIF, TIR-domain-containing adapter-inducing interferon-β; TBK1, TANK binding kinase 1; IRF, interferon regulatory factor; IFN-β, interferon-β; Gas6, growth arrest specific 6; Axl, AXL receptor tyrosine kinase; IFNAR, interferon alpha and beta receptor subunit; JAK, janus kinase; STAT, signal transducer and activator of transcription; ISRE, interferon-stimulated response element; GAS, gamma-activated sequence; SOCS1, suppressor of cytokine signaling 1; IFIH1, interferon induced with helicase c domain 1; CCL, C-C motif chemokine ligand; TMEM173, transmembrane protein 173; IFI, interferon inducible protein; ADAR, adenosine deaminase RNA specific; DDX58, DExD/H-box helicase 58; Mx, MX dynamin like GTPase; OAS, 2’−5’-oligoadenylate synthetase; CH25H, cholesterol 25-hydroxylase; IFITM, interferon induced transmembrane protein; IFIT, interferon induced protein with tetratricopeptide repeats; ISG20, interferon stimulated exonuclease gene 20; ISG15, ISG15 ubiquitin like modifier; Viperin/RSAD2, radical S-adenosyl methionine domain containing 2; Tetherin/BST2, bone marrow stromal cell antigen 2; TRAIL/TNFSF10, TNF superfamily member 10; FAS, Fas cell surface death receptor; CASP1, caspase 1; P, phosphorylation. Figure created with BioRender.com