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  • Research Summary of Keisa Mathis, PhD

    Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women at a 9:1 ratio over men. Patients with SLE have elevated levels of autoantibodies (e.g., anti-double-stranded DNA autoantibody) that form immune complexes and deposit into tissues to cause an inflammatory response. In the kidney the result is immune complex glomerulonephritis, which can promote impaired renal function, and potentially lead to the development of hypertension. Therefore, SLE is a major risk factor for renal disease and hypertension.

    Recently, a growing amount of data implicates an important role for chronic inflammation in the development of renal disease and hypertension by mechanisms that remain unclear. The autonomic nervous system plays an important role immune system regulation and therefore neuroimmune influences on the kidney could promote renal injury. Many patients with SLE have enhanced sympathetic nervous system (SNS) activity making it an ideal disease model to study neuroimmune mechanisms that promote renal injury and hypertension.

    The female NZBWF1 mouse is a genetic model of SLE created by crossing New Zealand White with New Zealand Black mice. The F1 females from this genetic cross exhibit many characteristics of SLE in humans including the production of characteristic autoantibodies and the development of immune complex glomerulonephritis. Our laboratory has also recently established the NZBWF1 female mice as a model of chronic inflammation with hypertension. Therefore, although this model has been studied for over 40 years, we have established this as a novel tool to investigate the mechanisms by which immune system dysfunction can lead to renal injury and hypertension.

    In my current study, we hypothesized that the renal sympathetic nerves contribute mechanistically to the development of renal injury and hypertension during chronic inflammatory disease. In order to test this, we performed a bilateral renal denervation in the NZBWF1 mouse. My data shows that the renal denervation ameliorates renal injury independently of changes in blood pressure and that this renal protection occurs likely as result of reduced renal inflammation.