The Changing Landscape of Renal Inflammation

Abstract

Kidney inflammation is a major contributor to progressive renal injury, leading to glomerulonephritis (GN) and chronic kidney disease. We review recent advances in our understanding of leukocyte accumulation in the kidney, emphasizing key chemokines involved in GN. We discuss features of renal inflammation such as the evolving concept of immune cell plasticity. We also describe certain aspects of organ-specific tissue microenvironments in shaping immune cell responses, as well as the current knowledge of how regulatory T lymphocytes impact on other immune effector cell populations to control inflammation. It is clear that present and future research in these areas may contribute to the development of novel targeted therapeutics, with the hope of alleviating the burden of end-stage renal disease (ESRD).

Keywords: chemokines; effector immune cells; environmental triggers; glomerulus; leukocyte recruitment; local inflammation; phenotype stability; regulatory immune cells.

Key Figure, Figure 1. Mechanisms Controlling Leukocyte Accumulation During Kidney Inflammation

Various triggers induce primary renal tissue injury that subsequently lead to the production of cytokines and chemokines from intrinsic renal cells. These inflammatory cues, dictated by the nature and the site of the initiating injury, coordinate leukocyte accumulation and the temporal infiltration of leukocyte subsets. Recruited leukocytes, in turn, influence the recruitment and activation of other immune cells. As well as the responses from renal cells. Recruited immunoregulatory cells eventually terminate the inflammatory response. Patrolling monocytes may also control inflammatory responses by maintaining endothelial integrity. Finally, the inflammatory microenvironment, influenced by exogenous factors such as high sodium diet, uremic toxins and microbiota (see text), define the inflammatory landscape and thus, leukocyte influx.