The Changing Landscape of Renal Inflammation

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).

TrendsLeukocyte recruitment in the specialized microvasculature of the renal glomerulus differs from the classical paradigm of leukocyte rolling, arrest, and transmigration.The local inflammatory microenvironment is largely defined by the local production of chemokines, which orchestrate leukocyte accumulation and can contribute to kidney dysfunction, as is the case in GN.Factors such as sodium levels, uremia, or changes in the microbiota may reset homeostatic equilibria in the kidney, thus influencing the immune response.Expanding subsets of immune regulatory cells help to maintain immune homeostasis. Regulatory T cells are particularly important in limiting inflammatory kidney damage.The concept of T cell plasticity has questioned some aspects of lineage commitment and terminal differentiation of leukocyte subsets.One of the challenges of targeted renal immunotherapy is attempting to balance and specifically elicit suppressive regulatory responses while inhibiting potentially damaging effector cell functions in the local kidney microenvironment.