The immunoregulatory roles of non-haematopoietic cells in the kidney

The deposition of immune complexes, activation of complement and infiltration of the kidney by cells of the adaptive and innate immune systems have long been considered responsible for the induction of kidney damage in autoimmune, alloimmune and other inflammatory kidney diseases. However, emerging findings have highlighted the contribution of resident immune cells and of immune molecules expressed by kidney-resident parenchymal cells to disease processes. Several types of kidney parenchymal cells seem to express a variety of immune molecules with a distinct topographic distribution, which may reflect the exposure of these cells to different pathogenic threats or microenvironments. A growing body of literature suggests that these cells can stimulate the infiltration of immune cells that provide protection against infections or contribute to inflammation - a process that is also regulated by draining kidney lymph nodes. Moreover, components of the immune system, such as autoantibodies, cytokines and immune cells, can influence the metabolic profile of kidney parenchymal cells in the kidney, highlighting the importance of crosstalk in pathogenic processes. The development of targeted nanomedicine approaches that modulate the immune response or control inflammation and damage directly within the kidney has the potential to eliminate the need for systemically acting drugs. Emerging evidence suggests that cells resident within organs - both immune and parenchymal - can facilitate the instigation and propagation of tissue injury. In this Review, the authors discuss findings that suggest that kidney parenchymal cells provide structural immunity to the kidney through the regulation of immune-relevant processes, with consequences for kidney inflammation and injury. Non-myeloid kidney parenchymal cells (KPCs) express molecules that are shared with immune cells; the expression of these molecules may have distinct topological associations and may increase in response to inflammation.Kidney injury can induce the infiltration of immune cells; these cells may have protective or pro-inflammatory features depending on the phase of the disease process. In addition, kidney-resident immune cells may have a surveillance or regulatory role in the kidney but can accumulate in response to injury.Components of the immune system, such as autoantibodies, cytokines and immune cells, can influence the metabolic profile of KPCs in the kidney.Conversely, KPCs can contribute to inflammation by providing metabolites or through the secretion of chemokines and cytokines.The cortex and the medulla of kidney tissue can contain distinct types of tertiary lymphoid organs, which may possess pathogenic or regulatory properties.Targeted delivery of drugs to KPCs holds promise for preventing or reversing the inflammatory response in specific forms of kidney injury and disease.