Targeting the Type I Interferon Pathway in Glomerular Kidney Disease: Rationale and Therapeutic Opportunities

Type I interferons (IFNs) are immunostimulatory molecules that can activate the innate and adaptive immune systems. In cases of immune dysfunction, prolonged activation of the type I IFN pathway has been correlated with kidney tissue damage in a wide range of kidney disorders, such as lupus nephriti...

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Main Authors: James Tumlin, Brad Rovin, Hans-Joachim Anders, Eduardo F. Mysler, David R.W. Jayne, Tsutomu Takeuchi, Catharina Lindholm, Gudrun Weiss, Alessandro Sorrentino, Kevin Woollard, Nicola Ferrari
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S246802492401979X
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Summary:Type I interferons (IFNs) are immunostimulatory molecules that can activate the innate and adaptive immune systems. In cases of immune dysfunction, prolonged activation of the type I IFN pathway has been correlated with kidney tissue damage in a wide range of kidney disorders, such as lupus nephritis (LN) and focal segmental glomerulosclerosis (FSGS). Genetic mutations, such as APOL1 risk variants in conjunction with elevated type I IFN expression, are also associated with higher rates of chronic kidney disease in patients with LN and collapsing FSGS. Long-term activation of the type I IFN pathway can result in chronic inflammation, leading to kidney tissue damage, cell death, and decline in organ function. Thus, therapeutic strategies targeting type I IFN could provide clinical benefits to patients with immune dysregulation who are at risk of developing impaired kidney function. Here, we present a critical review of type I IFN signaling, the consequences of chronically elevated type I IFN expression, and therapeutic strategies targeting type I IFN signaling in the context of kidney disease.
ISSN:2468-0249