Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy
Xiong T, Attar M, Gnirck AC, Wunderlich M, Becker M, Rickassel C, Puelles VG, Meyer-Schwesinger C, Wiech T, Nies JF, Divivier M, Fuchs T, Schulze zur Wiesch J, Taipaleenmäki H, Hoxha E, Wirtz S, Huber TB, Panzer U, Turner JE (2020)
Publication Type: Journal article
Publication year: 2020
Journal
DOI: 10.1016/j.kint.2020.04.036
Abstract
A wide spectrum of immunological functions has been attributed to Interleukin 9 (IL-9), including effects on the survival and proliferation of immune and parenchymal cells. In recent years, emerging evidence suggests that IL-9 expression can promote tissue repair in inflammatory conditions. However, data about the involvement of IL-9 in kidney tissue protection is very limited. Here, we investigated the role of IL-9 in Adriamycin-induced nephropathy (AN), a mouse model for proteinuric chronic kidney disease. Compared to wild type mice, IL-9 knockout (Il9−/−) mice with AN displayed accelerated development of proteinuria, aggravated glomerulosclerosis and deterioration of kidney function. At an early stage of disease, the Il9−/− mice already displayed a higher extent of glomerular podocyte injury and loss of podocyte number compared to wild type mice. In the kidney, T cells and innate lymphoid cells produced IL-9. However, selective deficiency of IL-9 in the innate immune system in Il9−/−Rag2−/− mice that lack T and B cells did not alter the outcome of AN, indicating that IL-9 derived from the adaptive immune system was the major driver of tissue protection in this model. Mechanistically, we could show that podocytes expressed the IL-9 receptor in vivo and that IL-9 signaling protects podocytes from Adriamycin-induced apoptosis in vitro. Finally, in vivo treatment with IL-9 effectively protected wild type mice from glomerulosclerosis and kidney failure in the AN model. The detection of increased serum IL-9 levels in patients with primary focal and segmental glomerulosclerosis further suggests that IL-9 production is induced by glomerular injury in humans. Thus, IL-9 confers protection against experimental glomerulosclerosis, identifying the IL-9 pathway as a potential therapeutic target in proteinuric chronic kidney disease.
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Germany (DE)How to cite
APA:
Xiong, T., Attar, M., Gnirck, A.C., Wunderlich, M., Becker, M., Rickassel, C.,... Turner, J.E. (2020). Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy. Kidney International. https://doi.org/10.1016/j.kint.2020.04.036
MLA:
Xiong, Tingting, et al. "Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy." Kidney International (2020).
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