TY - JOUR
T1 - Interferon regulatory factors
T2 - Critical mediators of human lupus
AU - Jensen, Mark A.
AU - Niewold, Timothy B.
N1 - Funding Information:
T.B. Niewold received research grants from the National Institutes of Health ( AR060861 , AI083790 , and AI071651 ), the Rheumatology Research Foundation , the Mayo Clinic Foundation , and the Lupus Foundation of Minnesota .
Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial, and the interferon regulatory factors (IRFs) play an important role. Autoantibodies formed in SLE target nuclear antigens, and immune complexes formed by these antibodies contain nucleic acid. These immune complexes can activate antiviral pattern recognition receptors (PRRs), resulting in the downstream activation of IRFs, which can induce type I interferon (IFN-I) and other inflammatory mediators. Genetic variations in IRFs have been associated with susceptibility to SLE, and current evidence supports the idea that these polymorphisms are gain of function in humans. Recent studies suggest that these genetic variations contribute to the break in humoral tolerance that allows for nucleic acid binding autoantibodies, and that the same polymorphisms also augment IFN-I production in the presence of these autoantibody immune complexes, forming a feed-forward loop. In this review, we will outline major features of the PRR/IRF systems and describe the role of the IRFs in human SLE pathogenesis.
AB - The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial, and the interferon regulatory factors (IRFs) play an important role. Autoantibodies formed in SLE target nuclear antigens, and immune complexes formed by these antibodies contain nucleic acid. These immune complexes can activate antiviral pattern recognition receptors (PRRs), resulting in the downstream activation of IRFs, which can induce type I interferon (IFN-I) and other inflammatory mediators. Genetic variations in IRFs have been associated with susceptibility to SLE, and current evidence supports the idea that these polymorphisms are gain of function in humans. Recent studies suggest that these genetic variations contribute to the break in humoral tolerance that allows for nucleic acid binding autoantibodies, and that the same polymorphisms also augment IFN-I production in the presence of these autoantibody immune complexes, forming a feed-forward loop. In this review, we will outline major features of the PRR/IRF systems and describe the role of the IRFs in human SLE pathogenesis.
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U2 - 10.1016/j.trsl.2014.10.002
DO - 10.1016/j.trsl.2014.10.002
M3 - Review article
C2 - 25445206
AN - SCOPUS:84921334545
SN - 1931-5244
VL - 165
SP - 283
EP - 295
JO - Translational Research
JF - Translational Research
IS - 2
ER -