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

To 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.

We 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.

Both 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.

Our 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.