Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

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Abstract

Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

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Physiological and pathological roles for microRNAs in the immune system.

Ryan O'Connell, Dinesh Rao, Aadel Chaudhuri … (2010)

Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression, and they function by repressing specific target genes at the post-transcriptional level. Now, studies of miRNAs are resolving some unsolved issues in immunology. Recent studies have shown that miRNAs have unique expression profiles in cells of the innate and adaptive immune systems and have pivotal roles in the regulation of both cell development and function. Furthermore, when miRNAs are aberrantly expressed they can contribute to pathological conditions involving the immune system, such as cancer and autoimmunity; they have also been shown to be useful as diagnostic and prognostic indicators of disease type and severity. This Review discusses recent advances in our understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated.

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Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy.

Juan F. Navarro-González, Carmen Mora-Fernández, Mercedes Muros de Fuentes … (2011)

Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus, modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today. The relationships between inflammation and the development and progression of diabetic nephropathy involve complex molecular networks and processes. This Review, therefore, focuses on key proinflammatory molecules and pathways implicated in the development and progression of diabetic nephropathy: the chemokines CCL2, CX3CL1 and CCL5 (also known as MCP-1, fractalkine and RANTES, respectively); the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion protein 1, endothelial cell-selective adhesion molecule, E-selectin and α-actinin 4; the transcription factor nuclear factor κB; and the inflammatory cytokines IL-1, IL-6, IL-18 and tumor necrosis factor. Advances in the understanding of the roles that these inflammatory pathways have in the context of diabetic nephropathy will facilitate the discovery of new therapeutic targets. In the next few years, promising new therapeutic strategies based on anti-inflammatory effects could be successfully translated into clinical treatments for diabetic complications, including diabetic nephropathy.

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The NOD mouse: a model of immune dysregulation.

Mark S. Anderson, Jeffrey Bluestone (2005)

Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.

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Journal

Journal ID (nlm-ta): J Clin Med

Journal ID (iso-abbrev): J Clin Med

Journal ID (publisher-id): jcm

Title: Journal of Clinical Medicine

Publisher: MDPI

ISSN (Electronic): 2077-0383

Publication date (Electronic): 19 January 2020

Publication date Collection: January 2020

Volume: 9

Issue: 1

Electronic Location Identifier: 272

Affiliations

[1 ]Laboratorio de Nefrología, Facultad de Medicina, Universidad Austral de Chile, Valdivia 5090000, Chile; carolavoz@ 123456gmail.com (C.L.); vmarchant.hernandez@ 123456gmail.com (V.M.); m.aledroguett@ 123456gmail.com (A.D.); mezzano.sergioa@ 123456gmail.com (S.M.)

[2 ]Vascular and Renal Translational Research Group, Institut de Recerca Biomèdica de Lleida (IRBLleida), 25198 Lleida, Spain; srayego@ 123456fjd.es

[3 ]Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, 28029 Madrid, Spain; macarena.orejudo@ 123456quironsalud.es (M.O.); laura.marqueze@ 123456quironsalud.es (L.M.-E.); antoniotemu@ 123456gmail.com (A.T.-M.); aortiz@ 123456fjd.es (A.O.);

[4 ]Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain

[5 ]Renal, Vascular and Diabetes Research Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain; lucasopazo78@ 123456gmail.com (L.O.-R.); jegido@ 123456fjd.es (J.E.)

[6 ]Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain

[7 ]Unidad de Investigación y Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain; jnavgon@ 123456gobiernodecanarias.org

[8 ]Nephrology and Hypertension, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, 28040 Madrid, Spain

Author notes

[* ]Correspondence: Mruizo@ 123456fjd.es

[†]

These authors contributed equally to this work as first author.

[‡]

These authors contributed equally to this work as senior author.

Author information

Lucas Opazo-Ríos https://orcid.org/0000-0003-3586-3319

Vanessa Marchant https://orcid.org/0000-0002-2767-0229

Juan F. Navarro-González https://orcid.org/0000-0002-5015-7474

Alberto Ortiz https://orcid.org/0000-0002-9805-9523

Raúl R. Rodrigues-Diez https://orcid.org/0000-0002-2456-6709

Marta Ruiz-Ortega https://orcid.org/0000-0002-1495-6535

Article

Publisher ID: jcm-09-00272

DOI: 10.3390/jcm9010272

PMC ID: 7019373

PubMed ID: 31963845

SO-VID: f1813f50-0d26-40a7-adb0-27f3f9b53625

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

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Wits Journal of Clinical Medicine

Most cited references 113

Physiological and pathological roles for microRNAs in the immune system.

Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy.

The NOD mouse: a model of immune dysregulation.

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