Editorial: Immune Landscape of Kidney Pathology

Abstract

Editorial on the Research Topic Immune Landscape of Kidney Pathology Kidney disease is an emerging cause of morbidity and mortality. More than 6 million patients worldwide receive renal replacement therapy. The global prevalence of chronic kidney disease (CKD) is between 11.7 and 15.1% of the adult population. Nevertheless, we still lack effective treatments to stop the progression of CKD, which makes it an urgent area with unmet clinical need. CKD is defined as abnormal kidney structure and/or function caused by primary and secondary glomerular diseases (including diabetes, hypertension, autoimmune diseases, etc.). Renal fibrosis is a common feature of CKD and is widely regarded as the main driver of the progression to end-stage renal disease. However, the underlying mechanisms of the renal fibrotic response are complex and still poorly understood. Emerging research shows that unresolved inflammation may be a necessary condition to promote the transition from acute kidney injury to chronic renal fibrosis. Various white blood cell populations are recruited into injured kidneys and play important roles in pathogen clearance and tissue repair. However, if this inflammatory response does not subside, it will instead promote progressive fibrosis of the damaged kidney. Interestingly, a large number of studies have shown that infiltrating leukocytes, including macrophages, dendritic cells, natural killer cells, and T and B cells, actively promote the transition from renal inflammation to fibrosis (Tang et al., 2020a). In addition, changes in the microenvironment in different kidney compartments also play a key role in the immune response and disease pathogenesis. A better understanding of the immune process in the development of CKD may reveal direct and indirect immunomodulation methods as new therapeutic strategies to prevent the progression of different forms of kidney disease. Therefore, we initiated this research project co-sponsored by Frontiers in Physiology and Frontiers in Medicine, aiming to bring together research from multiple disciplines, with special attention to immunology, renal physiology and pathology. We invited researchers to share their latest insights into how host immunity and its effectors reshape the kidney microenvironment to achieve the physiological and/or pathogenic effects of diseased kidneys. We are very pleased that this Research Topic has been welcomed by basic researchers and clinical scientists from all over the world. A total of 22 high-quality papers have been published, including nine original studies, six reviews, four mini-reviews, one case report and a brief research report. These papers are written by 159 authors from around the world, providing cross-sectional and multi-disciplinary approaches in the latest kidney disease research. Broadly speaking, these papers focus on five core topics: (i) immunodynamics; (ii) pathogenic mechanisms; (iii) advanced research technology; (iv) therapeutic development; and (v) social impact on patients with kidney disease. The following is a brief overview of each study. The kidney is one of the main organs for detoxification in our body. Its failure is an important cause of patient death. In addition, kidney disease is a major contributor to patient death in a wide range of diseases such as diabetes, cancer, bacterial and viral infections (including COVID-19; Tang et al., 2021a; Wang et al., 2021); leading to more than 6 million deaths worldwide each year. Thus, developing a better understanding, and treatment of, kidney disease is critical. Renal fibrosis is a key pathological mechanism in the loss of normal structure and function of the kidney, resulting in progressive kidney damage. Encouragingly, scientists have begun to realize that the over-activation of the immune system is an essential component in this process, and this feature is summarized by Tang et al. in this Research Topic. Macrophages are a type of immune cell that maintains the health of our kidneys (Tang et al., 2019). They are responsible for detecting, engulfing, and destroying pathogens and unhealthy cells as discussed by Cantero-Navarro et al. Paradoxically, new research finds that macrophages can also accelerate kidney failure as highlighted by a systematic review from Wang et al. A better understanding of the underlying mechanisms can isolate the adverse effects of macrophages from their protective effects. For example, a new phenomenon “macrophage-myofibroblast transition (MMT)” has been identified as a pathway promoting the tissue scarring (Figure 1), and dissecting this MMT pathway may identify novel druggable therapeutic targets for kidney fibrosis (Tang et al., 2018a, 2020b). Figure 1. Occurrence of MMT (yellow) in a human kidney with chronic allograft dysfunction, indicating by the presence of macrophage (CD68, red) expressing myofibroblast marker (alpha-SMA, green). Changes in the immune landscape are essential components in both disease pathogenesis and tissue repair in states of inflammation, but much remains to be done to fully describe such changes in kidney diseases. Vonbrunn et al. investigated the potential significance of glomerular immune reactivity for allograft survival by analyzing the immune profile of time zero kidney specimens and how this impact clinical outcomes. Albino et al. elucidated how innate immunity contributes to the transition of acute kidney injury to renal fibrosis in a gentamicin-induced renal inflammation model. Furthermore, Rodriguez-Carrio et al. found changes in several novel T cell and monocyte subsets during the progression of chronic kidney disease which were significantly associated with vascular outcomes. Unresolved renal inflammation can drive the progression of renal fibrosis, leading to end-stage renal disease. Understanding the mechanisms underlying this unrelenting renal fibrosis is critical for the development of new therapies...