Elucidating the function of STING in systemic lupus erythematosus through the STING Goldenticket mouse mutant

Sci Rep. 2024 Jun 17;14(1):13968. doi: 10.1038/s41598-024-64495-6.

Abstract

The complexity of systemic lupus erythematosus (SLE) arises from intricate genetic and environmental interactions, with STING playing a pivotal role. This study aims to comprehend the function of STING using the pristane-induced lupus (PIL) model in Sting missense mutant mice (Goldenticket or StingGt), which contrasts with previous research using Sting knockout mice. Investigating two-month-old StingGt mice over six months post-PIL induction, we observed a profound reduction in autoimmune markers, including antinuclear and anti-dsDNA antibodies, germinal center B cells, and plasma cells, compared to their wild-type counterparts. A pivotal finding was the marked decrease in IL-17-producing T cells. Notably, the severity of lupus nephritis and pulmonary hemorrhages was significantly diminished in StingGt mice. These findings demonstrate that different genetic approaches to interfere with STING signaling can lead to contrasting outcomes in SLE pathogenesis, which highlights the need for a nuanced understanding of the role of STING in drug development for SLE. In summary, the loss of Sting function in Goldenticket mutant mice rescued autoimmune phenotypes in PIL. This study reveals the critical nature of STING in SLE, suggesting that the method of STING modulation significantly influences disease phenotypes and should be a key consideration in developing targeted therapies.

Keywords: Mutation; Pristane-induced lupus; SLE; STING; Tmem173.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Disease Models, Animal*
  • Female
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Erythematosus, Systemic* / immunology
  • Lupus Erythematosus, Systemic* / pathology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / immunology
  • Lupus Nephritis / metabolism
  • Lupus Nephritis / pathology
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mutation, Missense
  • Terpenes

Substances

  • Membrane Proteins
  • Sting1 protein, mouse
  • pristane
  • Antibodies, Antinuclear
  • Terpenes
  • Interleukin-17