Biometal concentrations, distribution and re-distribution in the thymus of healthy mice and mice with inflammatory arthritis

Abstract

Background and objective

Zinc, iron and copper are important for the proper functioning of the immune system. The thymus has a critical role in autoimmune diseases. However, data on concentrations and spatial distribution of metal ions in the thymus are limited. We therefore aimed to investigate the essential metals zinc, iron, and copper, and the non-essential metal nickel in the thymus of healthy mice and two transgenic murine models that develop inflammatory arthritis resembling rheumatoid arthritis, an autoimmune disease.

Methods

In slices of thymus tissues from wild-type, TNFΔAREhTNFR1KI (spondyloarthritis model), and Tg197hTNFR1KI (polyarthritis model) mice, total metal analyses were performed with inductively coupled plasma mass spectrometry while metal imaging was performed with laser ablation inductively coupled plasma mass spectrometry with novel quality control, standardization, and procedures for statistical evaluation.

Results

Total metal analyses revealed no difference in zinc, but an about twofold increase of copper in the thymi of the diseased mice. Total iron and nickel concentrations were also increased in the TNFΔAREhTNFR1KI mice. Imaging showed a seemingly homogeneous distribution of zinc, copper, and nickel in all mice, while iron was more concentrated near the medulla/cortex boundary in the wild-type and Tg197hTNFR1KI mice. Concentration frequency distribution histograms revealed shifts in concentration ranges in inflammation.

Conclusion

Combining metal analyses and metal imaging with concentration frequency distribution histograms uncovered changes of metals in the thymus of mice with inflammatory arthritis. These observations underpin future mechanistic studies of the role of metals in the immunology of the thymus’ involvement in arthritic disease.