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 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.