Conclusion
We report, for the first time, the presence of p16Ink4a-positive cells, a marker of cellular senescence, in the B6.Sle1.2.3 kidney, and their association with renal disease severity. This provides a preclinical model in which to test for the role of cellular senescence in the pathogenesis of LN, as a potential kidney-intrinsic disease mechanism.
Methods
We evaluated the occurrence and time of onset of p16Ink4a staining by immunohistochemistry on kidney sections, and tested for its association with multiple renal and systemic disease parameters, fibrosis and CD8+ T cell infiltration, in two cohorts of B6.Sle1.2.3 mice.
Results
The presence of p16Ink4a-positive cells in kidney was significantly associated with increased urine albumin/creatinine ratio, histopathological scores, CD8+ T cell infiltration and fibrosis, in both B6.Sle1.2.3 cohorts. In contrast, p16Ink4a staining was not associated with systemic disease parameters. A time course showed that systemic disease parameters as well as glomerular IgG deposits appeared in B6.Sle1.2.3 mice by 4 months of age; the appearance of p16Ink4a-positive cells occurred later, by 8 months of age, overlapping with renal disease.