Effects of environmentally-induced anxiety on autoimmunity in the MRL/lpr mouse

• Published in: Lupus science & medicine Vol. 12; no. 1; p. e001528
• Main Authors: Zhang, Fan, Zhang, Qiong, Dang, Ruo-nan, Tian, Xiao-xue, Li, Lin-jie, Zhou, Quan-min, Li, Xiao-ying, Wu, Yuan-sheng, Zou, Hui-mei
• Format: Journal Article
• Language: English
• Published: England Lupus Foundation of America 19.06.2025; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Animal Models; Animals; Antibodies, Antinuclear - blood; Antibodies, Antinuclear - immunology; Anxiety - etiology; Anxiety - immunology; Anxiety disorders; Apoptosis; Autoimmunity - immunology; Chronic illnesses; Climate change; Disease; Disease Models, Animal; Female; Immune system; Inflammation; Interleukin-6 - blood; Lupus; Lupus Erythematosus, Systemic; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - psychology; Mental disorders; Mental health; Mice; Mice, Inbred MRL lpr; Mutation; Original Research; Pathogenesis; Physiology; Proteinuria; Psychology; Quality of life; Sleep; Spleen - immunology; Stress; Stress, Psychological - immunology; T-Lymphocytes, Regulatory - immunology; Th17 Cells - immunology; Lupus Erythematosus, Systemic; Psychology; Inflammation
• ISSN: 2053-8790; 2053-8790
• DOI: 10.1136/lupus-2025-001528

ObjectiveTo investigate the interplay between anxiety disorders and SLE using lupus-prone MRL-lpr mice and MRL/MPJ control mice exposed to predator stress, and to elucidate the potential mechanisms underlying this interaction.MethodsWe conducted an experiment where 16 MRL-lpr mice and 16 MRL/MPJ control mice were randomly assigned to four groups and exposed to predator stress (cat exposure) or served as unexposed controls for 2 months. Anxiety levels were evaluated using the elevated plus maze (EPM) and open field test (OFT). Physiological responses were assessed through measurements of body weight, interleukin-6 (IL-6) levels, anti-double-stranded DNA (dsDNA) antibody titres and urine protein content. Additionally, the splenic index and the proportions of regulatory T (Treg) and T helper 17 (Th17) cells were analysed to further understand the immune responses.ResultsBoth mouse strains exhibited increased anxiety levels as assessed by the EPM and OFT. However, MRL-lpr mice demonstrated a heightened sensitivity to predator stress-induced anxiety compared with MRL/MPJ mice. Biochemical analyses revealed that while MRL/MPJ mice showed a typical inflammatory response to predator stress, characterised by elevated IL-6 levels, this did not exacerbate immune dysregulation or renal damage. In contrast, MRL-lpr mice exhibited markedly increased IL-6 expression, elevated anti-dsDNA antibody levels, higher urine protein content, decreased Treg proportions and increased Th17 proportions in the spleen, suggesting an accelerated progression of lupus disease.ConclusionsOur findings emphasise that lupus-prone MRL-lpr mice display a greater vulnerability to the detrimental consequences of predator stress compared with MRL/MPJ control mice.