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Review 10.1172/JCI144918

Bite of the wolf: innate immune responses propagate autoimmunity in lupus

Sarthak Gupta and Mariana J. Kaplan

Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA.

Address correspondence to: Mariana J. Kaplan, Systemic Autoimmunity Branch, NIAMS/NIH, 10 Center Drive, 12N248C, Bethesda, Maryland 20892, USA. Phone: 301.496.0517; Email: mariana.kaplan@nih.gov.

Find articles by Gupta, S. in: JCI | PubMed | Google Scholar |

Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA.

Address correspondence to: Mariana J. Kaplan, Systemic Autoimmunity Branch, NIAMS/NIH, 10 Center Drive, 12N248C, Bethesda, Maryland 20892, USA. Phone: 301.496.0517; Email: mariana.kaplan@nih.gov.

Find articles by Kaplan, M. in: JCI | PubMed | Google Scholar

Published February 1, 2021 - More info

Published in Volume 131, Issue 3 on February 1, 2021
J Clin Invest. 2021;131(3):e144918. https://doi.org/10.1172/JCI144918.
© 2021 American Society for Clinical Investigation
Published February 1, 2021 - Version history
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The etiopathogenesis of systemic lupus erythematosus (SLE), a clinically heterogeneous multisystemic syndrome that derives its name from the initial characterization of facial lesions that resemble the bite of a wolf, is considered a complex, multifactorial interplay between underlying genetic susceptibility factors and the environment. Prominent pathogenic factors include the induction of aberrant cell death pathways coupled with defective cell death clearance mechanisms that promote excessive externalization of modified cellular and nuclear debris with subsequent loss of tolerance to a wide variety of autoantigens and innate and adaptive immune dysregulation. While abnormalities in adaptive immunity are well recognized and are key to the pathogenesis of SLE, recent findings have emphasized fundamental roles of the innate immune system in the initiation and propagation of autoimmunity and the development of organ damage in this disease. This Review focuses on recent discoveries regarding the role of components of the innate immune system, specifically neutrophils and interferons, in promoting various aspects of lupus pathogenesis, with potential implications for novel therapeutic strategies.

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