Role of STING Deficiency in Amelioration of Mouse Models of Lupus and Atherosclerosis

作者：Yudong Liu, Carmelo Carmona‐Rivera, Nickie Seto, Christopher B. Oliveira, Eduardo Patiño‐Martínez, Yvonne Baumer, Tiffany M. Powell‐Wiley, Nehal N. Mehta, Sarfaraz Hasni, Xuan Zhang, Mariana J. Kaplan · 发表于：Arthritis & Rheumatology · 年份：2024 · DOI：10.1002/art.43062 · 被引用次数：22 · 研究领域：interferon and immune responses、Systemic Lupus Erythematosus Research、Cytokine Signaling Pathways and Interactions

Objective Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome characterized by autoreactive responses to nucleic acids, dysregulation of the type I interferon (IFN‐I) pathway, and accelerated atherosclerosis. The stimulator of IFN genes (STING), a cytosolic DNA sensor, has pathogenic implications in various inflammatory diseases. However, its specific role in SLE pathogenesis, particularly in tissue damage, remains unclear. This study aimed to elucidate the role of STING in murine models of Toll‐like receptor 7 (TLR7)–driven lupus and atherosclerosis. Methods A TLR7‐driven lupus model was induced using imiquimod (IMQ) in wild‐type (WT) and STING knockout (Sting1 −/− ) mice on a B6 background. Mice were assessed for organ involvement, serum autoantibodies, and innate and adaptive immune responses. Additionally, Sting1 −/− mice were backcrossed to apolipoprotein E knockout (Apoe −/− ) mice, and both Apoe −/− and Apoe −/− Sting1 −/− mice were fed a high‐fat chow diet to induce atherosclerosis. Phenotypic assessments were conducted. Results Compared with IMQ‐treated WT mice, Sting1 −/− mice exhibited reduced disease severity in the lupus‐like phenotype, characterized by decreased splenomegaly, lower renal immune complex deposition and renal damage, diminished expansion of myeloid cells, and reduced activation of T and B lymphocytes. IMQ‐induced DNA release associated with IFN‐β production and subsequent IFN‐induced responses were attenuated in Sting1 −/− mice. DN...