Potential effects of interferon regulatory factor 4 in a murine model of polyinosinic-polycytidylic acid-induced embryo resorption
Jing Wang A , Tailang Yin A , Yanqi Wen A , Fuju Tian B , Xiaojun He A , Danni Zhou A , Yi Lin B C and Jing Yang A C
+ Author Affiliations
- Author Affiliations
A Department of Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, P. R. China.
B 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.
C Corresponding authors. Email: dryangjing108@163.com; yilinonline@126.com
Reproduction, Fertility and Development 28(10) 1631-1641 https://doi.org/10.1071/RD14499
Submitted: 15 December 2014 Accepted: 15 March 2015 Published: 15 April 2015
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.
Additional keywords: animal model, signal transduction, Th17 cell, Toll-like receptor 3.
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