title: Potential effects of interferon regulatory factor 4 in a murine model of polyinosinic-polycytidylic acid-induced embryo resorption.
abstract: Interferon regulatory factor (IRF) 4 has been reported to modulate Toll-like receptor (TLR) signalling. Polyinosinic-polycytidylic acid (poly(I:C)) can be specifically recognised by TLR3, triggering the innate immune response and subsequently resulting in pregnancy loss. In the present study, poly(I:C) was administered to mice with or without TLR3 blockade. Chemokine (C-X-C motif) receptor 4 (CXCR4) expression was measured with or without chemokine (C-X-C motif) ligand 12 (CXCL12) inhibition. In cultured murine splenic mononuclear cells, IRF4 was knocked down by a specific short interference (si) RNA. IRF4 mRNA and protein levels and T helper (Th) 17 cell frequencies in the poly(I:C)-treated group were significantly higher than in the phosphate-buffered saline (PBS)-treated control group, and were correlated with a significantly higher embryo resorption rate. Interleukin (IL)-17A and IL-21 levels were markedly lower in the IRF4 siRNA-treated group than in the non-specific siRNA- or vehicle control-treated groups. The CXCR4+ cell frequency was significantly higher among IRF4+ uterine mononuclear and granular cells (UMGCs) compared with IRF4- cells. Inhibition of CXCL12 significantly abrogated poly(I:C)-induced increases in the frequency of IRF4+CXCR4+ cells in UMGCs. IRF4 might play a critical role in TLR3 signalling, which mediates Th17 cell activation and upregulates the expression of IL-17A and IL-21, which results in pregnancy loss. CXCL12 may modulate IRF4+CXCR4+ cell migration at the fetomaternal interface. TLR3 and IRF4 blockade could potentially prevent spontaneous abortion under certain conditions.
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
authors: Jing
authors: J
authors: Wang
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
authors: Tailang
authors: T
authors: Yin
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
authors: Yanqi
authors: Y
authors: Wen
authors: Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, P. R. China.
authors: Fuju
authors: F
authors: Tian
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
authors: Xiaojun
authors: X
authors: He
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
authors: Danni
authors: D
authors: Zhou
authors: Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, P. R. China.|Corresponding authors. Email: dryangjing108@163.com.
authors: Yi
authors: Y
authors: Lin
authors: Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.|Corresponding authors. Email: dryangjing108@163.com.
authors: Jing
authors: J
authors: Yang
keywords: Th17 cell; Toll-like receptor 3; animal model; signal transduction