Interferon Regulation Factor‐3 is a Critical Regulator of the Mature of Dendritic Cells from Mice

Abstract

Interferon regulatory factor-3 (IRF-3) plays an important role in virus and double-stranded RNA-mediated induction of type I interferon and RANTES (regulated on activation normal T cell expressed and secreted), DNA damage signalling, tumour suppression and virus-induced apoptosis. IRF-3 had recently been shown to contribute to T-cell activation in response to pathogens, which implicated an extensive immunological role for IRF-3. Dendritic cells (DCs) played critical roles as professional APCs in the development of immune responses. However, it was unclear whether IRF-3 had any effect on phenotype or function of DCs. In this study, it was shown that IRF-3 acted as a promoter of DC maturation. The level of IRF-3 expression was transiently upregulated and accumulated in the nucleus in TNF-a-induced immune maturation of mice DC cells. Knockdown of IRF-3 by small interfering RNA in DC cells resulted in both phenotypic and functional immaturation, even without TNF-a treatment. Overall, our data demonstrated for the first time that IRF-3 was a critical regulator of mice DC maturation.

Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes

“…This optical reporter gene facilitates tracking of the initial distribution of these cells due to its high sensitivity 3 . Immortalized DC cell line (DC2.4) 4 has been well characterized and many researchers have applied it to immunologic research area 9 . For DC tracking study, DC2.4 cells simultaneously expressing a dual reporter gene system were established and used to employ both optical and nuclear molecular imaging.…”

Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses

“…IRF-3 expression is regulated by TBK1/IKKε in innate immune responses [30, 56]. Downregulation of IRF-3 in DCs by siRNA or drugs inhibited their phenotypic and functional maturation [31, 32], and irf3 −/− mice developed less severe EAE through reduced Th17 response [57]. Therefore, ALX may impede DC maturation and subsequent pro-inflammatory cytokine production, at least partially, through inhibiting the TBK1/IRF3 signaling, and further diminish effector T cell responses and EAE progression.…”

“…A recent study through ingenuity pathway analysis between semi-mature and fully mature DCs also reveals that TBK1 expression is upregulated in induced-matured DCs, suggesting its critical role in regulating DC maturation [29]. TBK1 can also phosphorylate and activate IRF-3, which acts as a promoter of DC maturation [30, 31]. Downregulating IRF-3 in DCs through small interfering RNA, or drugs such as zoledronic acid, results in both phenotypic and functional immaturity [31, 32].…”

“…TBK1 can also phosphorylate and activate IRF-3, which acts as a promoter of DC maturation [30, 31]. Downregulating IRF-3 in DCs through small interfering RNA, or drugs such as zoledronic acid, results in both phenotypic and functional immaturity [31, 32]. In addition, recent studies have indicated that activation of the TBK1/AKT signaling is necessary for TLR-driven glycolysis during DC activation, and inhibition of AKT can impede the activation and maturation of bone marrow DCs (BMDCs) [33].…”

Recombinant rabies virus expressing IFNα1 enhanced immune responses resulting in its attenuation and stronger immunogenicity

“…found to be essential for MAVS/IPS-1-directed ISG transcription and IFN-β secretion during virus infection (Sen et al, 2011;Zhang et al, 2013). As an important component of the type 1 IFN signaling pathway, STAT1 is widely expressed and thus most cell types are competent to mount type 1 IFN-dependent responses with other necessary components, such as IFNAR, JAK1, TYK2, STAT2, and IRF9.…”