Interleukin-9 protects from early podocyte injury and progressive glomerulosclerosis in Adriamycin-induced nephropathy
| Autor: | Tingting Xiong, Victor G. Puelles, Hanna Taipaleenmäki, Jasper F. Nies, Malte Wunderlich, Martina Becker, Tobias A. Fuchs, Ann-Christin Gnirck, Stefan Wirtz, Constantin Rickassel, Julian Schulze zur Wiesch, Ulf Panzer, Jan-Eric Turner, Elion Hoxha, Thorsten Wiech, Mylène Divivier, Madena Attar, Catherine Meyer-Schwesinger, Tobias B. Huber |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
030232 urology & nephrology Nephropathy Podocyte Mice 03 medical and health sciences 0302 clinical medicine Immune system Focal segmental glomerulosclerosis medicine Animals Humans Interleukin 9 Lymphocytes Glomerulosclerosis Focal Segmental Podocytes business.industry Innate lymphoid cell Interleukin-9 Glomerulosclerosis medicine.disease Immunity Innate Proteinuria 030104 developmental biology medicine.anatomical_structure Doxorubicin Nephrology Cancer research business Kidney disease |
| Zdroj: | Kidney International. 98:615-629 |
| ISSN: | 0085-2538 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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