Regulation of cGAS-STING Pathway - Implications for Systemic Lupus Erythematosus

Audrey M Hagiwara; Richard E Moore; Daniel J Wallace; Mariko Ishimori; Caroline A Jefferies

doi:10.2478/rir-2021-0023

Regulation of cGAS-STING Pathway - Implications for Systemic Lupus Erythematosus

Rheumatol Immunol Res. 2021 Dec 15;2(3):173-184. doi: 10.2478/rir-2021-0023. eCollection 2021 Sep.

Authors

Audrey M Hagiwara¹, Richard E Moore^{1

2}, Daniel J Wallace^{1

3}, Mariko Ishimori^{1

3}, Caroline A Jefferies^{1

2}

Affiliations

¹ Division of Rheumatology, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA, USA.
² Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA, USA.
³ Department of Medicine, David Geffen Medical School, University of California Los Angeles (UCLA), Los Angeles, CA, USA.

Abstract

Type I interferon (IFN-I) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and the closely associated monogenic autoinflammatory disorders termed the "interferonopathies." Recently, the cytosolic DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have been identified as having important, if not central, roles in driving IFN-I expression in response to self-DNA. This review highlights the many ways in which this pathway is regulated in order to prevent self-DNA recognition and underlines the importance of maintaining tight control in order to prevent autoimmune disease. We will discuss the murine and human studies that have implicated the cGAS-STING pathway as being an important contributor to breakdown in tolerance in SLE and highlight the potential therapeutic application of this knowledge for the treatment of SLE.

Keywords: STING; cGAS; systemic lupus erythematosus; type I interferon.

Publication types

Review