9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      New insights into the role of renal resident cells in the pathogenesis of lupus nephritis

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. The immunopathogenesis of SLE is complex and most clinical trials of biologics targeting immune cells or their mediators have failed to show efficacy in SLE patients. It has therefore become increasingly clear that additional, local factors give rise to the inflammation and organ damage. In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          The immune system and kidney disease: basic concepts and clinical implications.

          The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective.

            Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors. Novel observations have provided an improved understanding of the contribution of tissue-specific factors and associated damage, T and B lymphocytes, as well as innate immune cell subsets and their corresponding abnormalities. The intricate web of involved factors and pathways dictates the adoption of tailored therapeutic approaches to conquer this disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Induction of B7-1 in podocytes is associated with nephrotic syndrome.

              Kidney podocytes and their slit diaphragms form the final barrier to urinary protein loss. This explains why podocyte injury is typically associated with nephrotic syndrome. The present study uncovered an unanticipated novel role for costimulatory molecule B7-1 in podocytes as an inducible modifier of glomerular permselectivity. B7-1 in podocytes was found in genetic, drug-induced, immune-mediated, and bacterial toxin-induced experimental kidney diseases with nephrotic syndrome. The clinical significance of our results is underscored by the observation that podocyte expression of B7-1 correlated with the severity of human lupus nephritis. In vivo, exposure to low-dose LPS rapidly upregulates B7-1 in podocytes of WT and SCID mice, leading to nephrotic-range proteinuria. Mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, suggesting a link between podocyte B7-1 expression and proteinuria. LPS signaling through toll-like receptor-4 reorganized the podocyte actin cytoskeleton in vitro, and activation of B7-1 in cultured podocytes led to reorganization of vital slit diaphragm proteins. In summary, upregulation of B7-1 in podocytes may contribute to the pathogenesis of proteinuria by disrupting the glomerular filter and provides a novel molecular target to tackle proteinuric kidney diseases. Our findings suggest a novel function for B7-1 in danger signaling by nonimmune cells.
                Bookmark

                Author and article information

                Journal
                Korean J Intern Med
                Korean J. Intern. Med
                KJIM
                The Korean Journal of Internal Medicine
                The Korean Association of Internal Medicine
                1226-3303
                2005-6648
                March 2018
                12 January 2018
                : 33
                : 2
                : 284-289
                Affiliations
                [1 ]Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
                [2 ]Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
                Author notes
                Correspondence to George C. Tsokos, M.D. Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS937, Boston, MA 02115, USA Tel: +1-617-735-4161 Fax: +1-617-735-4170 E-mail: gtsokos@ 123456bidmc.harvard.edu
                Article
                kjim-2017-383
                10.3904/kjim.2017.383
                5840601
                29320847
                64db2f1b-11dd-455d-8527-070ff3d4931e
                Copyright © 2018 The Korean Association of Internal Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 November 2017
                : 4 December 2017
                Categories
                Review

                Internal medicine
                systemic lupus erythematosus,autoimmune diseases,lupus nephritis,podocytes
                Internal medicine
                systemic lupus erythematosus, autoimmune diseases, lupus nephritis, podocytes

                Comments

                Comment on this article