Type I Interferon in the Pathogenesis of Lupus
Top Cited Papers
Open Access
- 15 June 2014
- journal article
- review article
- Published by The American Association of Immunologists
- Vol. 192 (12), 5459-5468
- https://doi.org/10.4049/jimmunol.1002795
Abstract
Investigations of patients with systemic lupus erythematosus have applied insights from studies of the innate immune response to define IFN-I, with IFN-α as the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I–signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFN-I–induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained antivirus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients.Keywords
This publication has 123 references indexed in Scilit:
- Autoimmunity Initiates in Nonhematopoietic Cells and Progresses via Lymphocytes in an Interferon-Dependent Autoimmune DiseaseImmunity, 2012
- Toll-like receptor driven B cell activation in the induction of systemic autoimmunitySeminars in Immunology, 2011
- A loss‐of‐function variant of the antiviral molecule MAVS is associated with a subset of systemic lupus patientsEMBO Molecular Medicine, 2011
- Interferon‐α accelerates murine systemic lupus erythematosus in a T cell–dependent mannerArthritis & Rheumatism, 2010
- Interferon‐regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation studyArthritis & Rheumatism, 2009
- Age- and gender-specific modulation of serum osteopontin and interferon-α by osteopontin genotype in systemic lupus erythematosusGenes & Immunity, 2009
- Trex1 Prevents Cell-Intrinsic Initiation of AutoimmunityCell, 2008
- Association of the IRF5 risk haplotype with high serum interferon‐α activity in systemic lupus erythematosus patientsArthritis & Rheumatism, 2008
- A Modular Analysis Framework for Blood Genomics Studies: Application to Systemic Lupus ErythematosusImmunity, 2008
- Toll-like Receptor 7 and TLR9 Dictate Autoantibody Specificity and Have Opposing Inflammatory and Regulatory Roles in a Murine Model of LupusImmunity, 2006