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Self versus non-self discrimination is a critical step in the induction of innate immune responses that clear infections. These innate immune responses are an organism’s first-line of defense against microbial infections. When these responses are dysregulated, it can lead to auto-immunity. RIG-I is a pathogen recognition receptor (PRR) that can sense the presence of non-self viral RNA in an infected cell and can establish innate immune programs which limit and restrict RNA virus infections.
Figure 1. The RLR pathway is responsive to diverse stimuli to drive innate immunity.
RIG-I-like receptors (RLR) are cytoplasmic pathogen recognition receptors which detect pathogen-associated molecular patterns (PAMP) within viral RNA. There are three main members of the RLR family, RIG-I (retinoic acid inducible gene-I), LGP2 (Laboratory of genetics and physiology 2) and MDA5 (melanoma differentiation associated gene 5). The RLRs are broadly expressed in multiple cell types and in a number of tissues to assist with pathogen recognition. The expression of the RLRs remains at low levels in the steady-state and is greatly increased upon IFN exposure or in response to virus infection. RIG-I is the prototypical RLR that is indispensable for recognition of many RNA viruses by the binding of viral RNA which initiates innate immune responses and antiviral programs that control RNA virus infections. RIG-I signaling results in the activation of transcription factors (such as AP1, IRF3/7, and NF-κB), production of type I interferons (type-I IFN), secretion of proinflammatory cytokines and drives the expression of innate immune genes. Immune responses induced by type-I IFNs are important in triggering innate antiviral responses through Janus kinases and signal transducer and activator of transcription protein (JAK-STAT) signaling pathway.
Increasing evidence suggests that aberrant IFN induction and the resulting signaling of innate immune programs is associated with autoimmune disease. Because they are receptors that regulate IFN induction, there is increasing interest in assessing potential links between RLR function and/or polymorphisms that could lead to differences in susceptibility to infection and predispositions to autoimmune diseases. Silencing of MDA5 expression in rat pancreatic b cells by siRNA treatment reduced poly(I:C) induced expression of proinflammatory cytokine and IFN, suggesting that aberrant interferon induction through MDA5 may be a factor in b cell programming of T1D. Besides its linkage with T1D, MDA5 was recently identified as the 140 kDa autoantigen most frequently associated with clinical amyopathic dermatomyositis. Subjects that exhibit an accumulation of autoantibodies to MDA5 are often associated with a higher frequency of rapidly progressive interstitial lung disease. In addition, a loss-of-function polymorphism of IPS-1 that resulted in the expression of a nonfunctional IPS-1 variant expected to abrogate RLR signaling has been linked to a subtype of systemic lupus erythematosus.
RLRs are crucial pathogen recognition receptors that impart recognition of RNA virus infection. RLR signaling activation by ligand interaction serves to initiate the immune response to virus infection, hence an increased understanding of the molecular features underlying these processes could provide new strategies to consider for immune and antiviral therapy through targeting the RLR pathway for the therapeutic control of virus infection and enhancement of the immune response, and strategies of immune suppression to control inflammation or specific autoimmune diseases. Creative Biogene is able to offer various RIG-I-LIKE receptor signaling pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.
RIG-I-LIKE Receptor Signaling Pathway Product Panel
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