Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes

Abstract

Accumulating evidence indicates that inflammatory and immunologic processes play a significant role in the development and progression of glomerular diseases. Podocytes, the terminally differentiated epithelial cells, are crucial for maintaining the integrity of the glomerular filtration barrier. Once injured, podocytes cannot regenerate, leading to progressive proteinuric glomerular diseases. However, emerging evidence suggests that podocytes not only maintain the glomerular filtration barrier and are important targets of immune responses but also exhibit many features of immune-like cells, where they are involved in the modulation of the activity of innate and adaptive immunity. This dual role of podocytes may lead to the discovery and development of new therapeutic targets for treating glomerular diseases. This review aims to provide an overview of the innate immunity mechanisms involved in podocyte injury and the progression of proteinuric glomerular diseases.

Keywords: STING; TLRs; glomerular disease; inflammation; innate immunity; podocyte.

Figure 1

Contribution of the innate immune system to glomerular disease pathogenesis. Current knowledge suggests that many molecules of innate immunity are involved in the pathogenesis of glomerular diseases. AS—Alport Syndrome; CD80—cluster of differentiation 80; DC-SIGN—dendric-cell-specific intracellular adhesion molecule-3-grabbing non-integrin; DKD—diabetic kidney disease; FD—Fabry disease; FSGS—focal segmental glomerulosclerosis; MCD—minimal change disease; MDA5—melanoma differentiation-associated gene 5; MN—membranous nephropathy; NLRP3—NLR family pyrin domain-containing 3; RIG-I—retinoic acid-inducible gene I; STING—stimulator of interferon genes; TLR—toll-like receptor.