ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0497

Interleukin-23 Acts Directly on Podocytes and Contributes to the Development of Glomerulonephritis

Shui Lian Yu1, Hao Li1, Abhigyan Satyam1, Shawn Rose2, Jarrat Jordan3 and George Tsokos4, 1Division of Rheumatology & Clinical Immunology/Beth Israel Deaconess Medical Center/Harvard Medical School, boston, 2Rheumatology & Autoimmunity Translational Medicine at Janssen Pharmaceuticals, boston, 3Janssen Research & Development, LLC, Spring House, PA, 4Division of Rheumatology & Clinical Immunology/Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA

Meeting: ACR Convergence 2020

Keywords: ,

Session Information

Date: Friday, November 6, 2020

Title: SLE – Etiology & Pathogenesis (0494–0498)

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.   

Disclosure: S. Yu, None; H. Li, None; A. Satyam, None; S. Rose, Janssen, 1, 3; J. Jordan, Janssen Research & Development, LLC, 1, 3; G. Tsokos, None.

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 .

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-23-acts-directly-on-podocytes-and-contributes-to-the-development-of-glomerulonephritis/