Characterization of the kidney immune niche in a mouse model of lupus

Details

Supervisors

Stockis, Julie

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

enLupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), a common autoimmune disease. Despite therapeutic advances, current treatments often remain insufficient to prevent irreversible renal damage, highlighting the need for a better understanding of LN pathogenesis. Among the various immune cell populations involved, type-2 innate lymphoid cells (ILC2s) have recently attracted increasing interest in the context of kidney diseases. In the MRL/lpr mouse model of lupus, renal ILC2s are reduced, and their restoration improves survival. Moreover, in inflammatory context, ILC2s are known to interact with regulatory T lymphocytes (Tregs), which are essential for the maintenance of immune tolerance, via OX40L-OX40 signalling. In this study, we characterized the renal immune niche in SLE123 mice, a spontaneous lupus model that faithfully reproduces the features of the human disease, with particular attention to the early stages of the disease. Using full-spectrum flow cytometry, we unexpectedly identified an increase in the absolute number of renal ILC2s with age, leading us to explore their potential role in disease progression. We observed that high ILC2 numbers were particularly evident in mice exhibiting the most severe signs of the disease. Nonetheless, their production of type-2 cytokines remained unaffected. Furthermore, neither an increase in alarmins known to activate ILC2s, nor enhanced proliferation or migration, could explain their accumulation with age in SLE123 mice. In parallel, we explored the possibility of a functional dialogue between ILC2s and Tregs via OX40L-OX40 signalling, as Tregs were also increased in old SLE123 mice and localized within the same renal immune niche. Although renal ILC2s displayed limited OX40L expression, conventional type-2 dendritic cells (cDC2s) emerged as a major source of OX40L in SLE123 mice, thereby opening new avenues for future research. Overall, these results reveal a profound immunological remodelling of the renal immune niche in SLE123 mice as early as 5-6 months of age.