TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction

Oshiumi, Hiroyuki; Matsumoto, Misako; Funami, Kenji; Akazawa, Takashi; Seya, Tsukasa

doi:10.1038/ni886

Cited by 1,083 publications

(894 citation statements)

References 40 publications

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“…2a). On the other hand, pufferfish TLR3 expression was limited to the liver and digestive organs (Oshiumi et al 2003b). GrTLR3 expression in liver and intestine was much higher than that in other tissues after stimulation (Fig.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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Toll-like receptor 3 (TLR3) plays a key role in activating immune responses during viral infection. To study the genes involved in the regulatory function of TLR3 in the rare minnow Gobiocypris rarus after viral infection, a full-length cDNA of TLR3 (GrTLR3) with a splice variant (GrTLR3s) was identified by homologous cloning and RACE techniques. The antiviral effector molecule Mx gene was cloned and partially sequenced. The mRNA expression levels of GrTLR3, GrTLR3s, and Mx were studied in different tissues before and after virus infection by real-time quantitative RT-PCR. The transcripts of all three genes in liver were significantly increased following GCRV infection (P<0.05). The mRNA levels in liver were upregulated at 24 h post-injection for GrTLR3 and GrTLR3s, and at 12 h for Mx. The upregulated expression levels were several folds for GrTLR3s, tens of folds for GrTLR3, and hundreds of folds for Mx. By semiquantitative RT-PCR, GrTLR3 and Mx expressed at all the developmental stages, whereas GrTLR3s could only be detected at later developmental stages. Using RNAi and transgenic techniques, GrTLR3 mediated Mx expression but GrTLR3s did not. The time-dependent upregulation of receptor and effector, and the Mx over-expression dependent on TLR3, indicated that GrTLR3 regulated Mx expression in viral infection through a configuration change in rare minnow, and its splice variant did not contribute to the process.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 3 regulates Mx expression in rare minnow Gobiocypris rarus after viral infection

Zhang

Wang

et al. 2008

Immunogenetics

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“…It is selectively expressed on a subpopulation of immature dendritic cells that have been implicated in inducing immune responses (12). In addition to delivering MyD88-dependent signals typical of most TLRs, TLR-3 can also trigger a non-MyD88-dependent signaling pathway that induces secretion of type I interferons (11), which have been particularly implicated in the development of autoimmunity (13). Furthermore, we have shown that TLR-3 but not TLR-5 induces high levels of IL-6 secretion; this is notable because IL-6 can block the suppressor activity of CD4ϩ,CD25ϩ T cells (14).…”

Section: Discussionmentioning

confidence: 99%

“…flagellin is thought to be strictly MyD88 dependent (10), while TLR-3 signals through both MyD88-dependent and MyD88-independent pathways (11). We observed that in RL-95 cells, flagellin induced high levels of IL-8 secretion but substantially lower levels of IL-6 secretion, while poly(I-C) and U1 RNA induced levels of IL-6 secretion that were equal to or greater than levels of IL-8 secretion ( Figure 2C).…”

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confidence: 99%

U1 RNA induces innate immunity signaling

Hoffman

Gazitt

Foecking

et al. 2004

Arthritis & Rheumatism

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Objective. The U1-70-kd RNP is a prominent target of autoimmunity in connective tissue diseases. In this study, we explored whether its endogenous ligand, U1 RNA, mediates a proimmune signal and may be immunogenic.Methods. We assayed the proliferation of control and MyD88-knockout splenocytes in response to in vitro-synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced by U1 RNA in a human cell line competent for signaling through Tolllike receptor 3 (TLR-3) and TLR-5. Conclusion. U1 RNA is capable of inducing manifestations consistent with TLR-3 activation. The ability of U1 RNA (which has a substantial double-stranded secondary structure) to activate TLR-3 may contribute to the immunogenicity of the U1-70-kd autoantigen.Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.

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“…When cells are stimulated through TLR3 and TLR4, TRIF (TICAM-1), a TIR-domain containing adapter, mediates activation of NF-kB in the absence of MyD88 (Oshiumi et al, 2003). Furthermore, in the case of TLR3, all downstream signaling appears to be TRIFdependent.…”

Section: Toll-like Receptorsmentioning

confidence: 99%