A compass that points to lupus: genetic studies on type I interferon pathway

Kyogoku, Chieko; Tsuchiya, Naoyuki

doi:10.1038/sj.gene.6364409

Cited by 85 publications

(80 citation statements)

References 107 publications

(143 reference statements)

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“…In humans, increased serum levels of type I IFNs have been described in lupus patients where type I IFN signaling is thought to promote the maturation of DCs, resulting in enhanced T cell activation (38). Interestingly, polymorphisms in the type I IFN pathway are associated with disease susceptibility (39).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Allograft Tolerance by Bacterial Infection with Listeria monocytogenes

Wang¹,

Chen

Ahmed³

et al. 2008

The Journal of Immunology

101

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Exposure to certain viruses and parasites has been shown to prevent the induction of transplantation tolerance in mice via the generation of cross-reactive memory T cell responses or the induction of bystander activation. Bacterial infections are common in the perioperative period of solid organ allograft recipients in the clinic, and correlations between bacterial infections and acute allograft rejection have been reported. However, whether bacterial infections at the time of transplantation have any effect on the generation of transplantation tolerance remains to be established. We used the Gram-positive intracellular bacterium Listeria monocytogenes (LM) as a model pathogen because its effects on immune responses are well described. Perioperative LM infection prevented cardiac and skin allograft acceptance induced by anti-CD154 and donor-specific transfusion in mice. LM-mediated rejection was not due to the generation of cross-reactive T cells and was largely independent of signaling via MyD88, an adaptor for most TLRs, IL-1, and IL-18. Instead, transplant rejection following LM infection was dependent on the expression of the phagosome-lysing pore former listeriolysin O and on type I IFN receptor signaling. Our results indicate that bacterial exposure at the time of transplantation can antagonize tolerogenic regimens by enhancing alloantigen-specific immune responses independently of the generation of cross-reactive memory T cells.

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Section: Discussionmentioning

confidence: 99%

Prevention of Allograft Tolerance by Bacterial Infection with Listeria monocytogenes

Wang¹,

Chen

Ahmed³

et al. 2008

The Journal of Immunology

101

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“…IC from SLE patients mixed with apoptotic cells or purified autoantigens induces type I IFN from murine DCs by a mechanism that involves FcγRIIA internalization and delivery of autoantigens to intracellular TLR7 and TLR9 (23,46). Type I IFN, in turn, promotes the activation of autoreactive B cells by enhancing B-cell survival, inducing TLR7 expression, and triggering secretion of IgG2a (21,47). As IRF5 is required for IC-mediated type I IFN expression by DCs and for IgG2a secretion by B cells, our system cannot experimentally determine which of the two is more critical for SLE disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…A potential role for IRF5 in SLE pathogenesis in humans is indicated by the observation that several polymorphisms that increase IRF5 mRNA stability and protein abundance raise the susceptibility to develop SLE (19,20). In view of IRF5's ability to regulate the induction of type I IFNs and the involvement of type I IFNs in the pathogenesis of SLE, the current conventional wisdom is that IRF5 may drive SLE development by causing the aberrant production of type I IFN through TLR9 and/or TLR7 signaling activated by ICs (21,22). This is supported by the ample genetic evidence that TLR7 and TLR9 are involved in the development of lupus-like disease in mice.…”

mentioning

confidence: 99%

Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus

Savitsky

Yanai

Tamura

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Interferon regulatory factor (IRF) 5 is a key transcription factor for the activation of innate immune responses downstream of Tolllike receptor signaling. Based on recent genetic analyses, IRF5 is a focus for its potential involvement in systemic lupus erythematosus (SLE), although how IRF5 contributes to SLE is uncertain. In this study, we demonstrate a requirement for IRF5 in the development of murine SLE via its role in B lymphocytes. We show that antinuclear autoantibodies and Ig glomerular deposits, hallmarks of SLE, are absent in Irf5 −/− mice challenged to develop SLE by pristane injection. In particular, production of autoantibodies of the IgG2a subtype, the most prominent isotype in inducing autoimmunity, requires IRF5. Finally, we provide evidence for the critical role of this transcription factor in the secretion of pathogenic antibodies through its direct control of class switch recombination of the γ2a locus. By demonstrating a B-cell-intrinsic role, this study places IRF5 in a context that may have implications for understanding the pathogenesis of human SLE.autoimmunity | B lymphocytes | TLR signaling

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“…See text for more details and references. Graham et al, 2007; Kozyrev et al, 2007;Kyogoku & Tsuchiya, 2007) and arthritis (Sigurdsson et al, 2007). , 2006).…”

Section: Induction Of Ifn By Virusesmentioning

confidence: 99%

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

Randall

Goodbourn

2008

Journal of General Virology

1,387

1,420

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The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer. Biology of the interferon systemThe interferons (IFNs) are a group of secreted cytokines that elicit distinct antiviral effects. They are grouped into three classes called type I, II and III IFNs, according to their amino acid sequence. Type I IFNs (discovered in 1957;Isaacs & Lindenmann, 1957) comprise a large group of molecules; mammals have multiple distinct IFN-a genes (13 in man), one to three IFN-b genes (one in man) and other genes, such as IFN-v, -e, -t, -d and -k. The IFN-a and -b genes are induced directly in response to viral infection, whereas IFN-v, -e, -d and -k play less well-defined roles, such as regulators of maternal recognition in pregnancy. Thus, rather than use the term 'type I IFN', we will use IFN-a/b when referring to the virally induced cytokines. Although the multigenic nature of IFN-a has been known for over 20 years, the significance of this is still debatedi.e. whether these genes are expressed differentially in distinct cell types, whether they are inducible by different types of viruses or whether they are functionally specialized (Brideau-Andersen et al., 2007). For the rest of this review, we will not distinguish between IFN-a subtypes. Type III IFNs have been described more recently and comprise IFNl1, -l2 and -l3, also referred to as IL-2...

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A compass that points to lupus: genetic studies on type I interferon pathway

Cited by 85 publications

References 107 publications

Prevention of Allograft Tolerance by Bacterial Infection with Listeria monocytogenes

Prevention of Allograft Tolerance by Bacterial Infection with Listeria monocytogenes

Contribution of IRF5 in B cells to the development of murine SLE-like disease through its transcriptional control of the IgG2a locus

Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures

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