The prevalence of autoimmune diseases continues to rise, yet many factors underlying their development remain poorly understood. Systemic lupus erythematosus (SLE) is a common and well-studied autoimmune disease, with several established mouse models available for its investigation. While the genetic predispositions for SLE are well characterized, it is still unclear how the immune system changes during the period preceding the clinical onset of the disease.

This thesis aims to characterize immunological and phenotypic changes in lupus-prone SLE123 and NZM2410 mice during this so-called pre-disease phase.

In addition, several external triggers are known to provoke lupus flares, with ultraviolet (UV) light being a prominent example. Although everyone is exposed to sunlight in daily life, individuals predisposed to lupus may mount a different immunological response compared to healthy individuals. Since the UV spectrum includes a range of wavelengths that penetrate the skin at varying depths, it is crucial to dissect these effects in detail.

Objectives

1. Perform deep immunophenotyping of lupus-prone mice during the pre-disease phase.

2. Assess movement, fluctuations in body and spleen weight, kidney function, and hematological parameters of lupus-prone mice in the pre-disease phase.

3. Investigate the effects of ultraviolet light exposure as a disease trigger on the skin of lupus-prone mice.

Work Program

To address objectives 1 and 2, cohorts of SLE123 and NZM2410 mice aged 8–20 weeks will be monitored weekly using flow cytometry, hematology, and microscopy, with a focus on T cells and selected maturation markers.

For objective 3, the skin of lupus-prone NZM2410 mice during the pre-disease phase will be irradiated with UVA, UVB, UVC, and selected blue light wavelengths to characterize their specific immunological effects. Skin mRNA will be sequenced, and immunohistochemical staining will be performed to validate the sequencing findings.