Session Type: Abstract Session
Session Time: 5:00PM-5:50PM
Background/Purpose: Interleukin (IL)-23 is central in the advancement of an inflammatory response and has been shown to be involved in the pathogenesis of autoimmune diseases. Therapeutic targeting of IL-23-mediated signaling is being exploited for therapeutic purposes. It is still unknown whether IL-23 can affect the function of tissue resident cells and promote organ damage. Disruption of podocyte structure and function represents a common feature of several inflammatory kidney diseases.
Methods: Podocytes were cultured on an advanced decellularized matrix (doi.org/10.1002/adfm.201908752).
Results: Using podocytes cultured on an advanced decellularized matrix, we demonstrated that in the presence of IL-23 the expression of IL-23 receptor on the surface membrane of podocytes increases significantly followed by increased levels of phosphorylated STAT3. We found that phosphorylated STAT3 associated with Rac1 and this resulted in decreased actin and synaptopodin, two proteins which are important in the structure of podocytes. Using a wound healing assay we showed that the presence of IL-23 increases the motility of podocytes. The presence of a small drug inhibitor of STAT3 prevented all aspects of IL-23-induced podocyte injury.
To determine the role of IL-23-instigated signaling in podocytes in the development of glomerulonephritis we constructed a mouse which lacked IL-23 receptor in podocytes (Il-23f/f.Nphs2cre) and exposed it to a nephrotoxic serum. Il-23f/f.Nphs2cremice, unlike control mice, developed minimal proteinuria, histologically defined glomerulonephritis and maintained normal levels of synaptopodin in their podocytes.
Conclusion: Our results present first evidence that IL-23 acts directly on tissue resident cells and contributes directly to the development of kidney disease. We propose that approaches to block IL-23 signaling should benefit people with glomerulonephritis.
To cite this abstract in AMA style:Yu S, Li H, Satyam A, Rose S, Jordan J, Tsokos G. Interleukin-23 Acts Directly on Podocytes and Contributes to the Development of Glomerulonephritis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/interleukin-23-acts-directly-on-podocytes-and-contributes-to-the-development-of-glomerulonephritis/. Accessed August 3, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-23-acts-directly-on-podocytes-and-contributes-to-the-development-of-glomerulonephritis/