Ischemia/reperfusion (IR) injury is the primary etiological factor for acute kidney injury (AKI) and a significant contributor to the negative impact on the development of chronic graft nephropathy. Recent studies have shown that IR injury triggers an inflammatory response involving various cells and molecules of the immune system. We are interested in studying the role of Toll-like receptors, Nod-like receptors, and inflammasomes, specifically focusing on the involvement of T lymphocytes, neutrophils, and macrophages in the pathogenesis of this injury. Our results demonstrate that the TLR4, NOD1, and NLRP3 pathways are early participants in the initial renal injury and that the CD4+ Th1 T lymphocyte subtype is the main aggressor in this injury.

Heme oxygenase 1 (HO-1) is considered a protective gene with anti-apoptotic, anti-proliferative, and anti-inflammatory activities. Overexpression of HO-1 in kidneys subjected to ischemia-reperfusion (IR) limits the damage caused by ischemia. In experimental models of chronic rejection, HO-1 can suppress atherosclerotic lesions, which are pathognomonic of chronic injury. However, the expression of HO-1 can be regulated by a polymorphism in its promoter and by the use of immunosuppressants. Our laboratory is interested in studying the role of HO-1 in acute kidney injuries and in various clinical situations post-kidney transplant, using in vitro models of epithelial-mesenchymal transdifferentiation and in vivo models of acute kidney injury.

The zebrafish (Danio rerio) offers numerous advantages as an experimental model. This fish has the fascinating characteristic of external fertilization with transparent eggs that develop rapidly, forming a complete embryo within 24 hours of fertilization. The zebrafish’s high regenerative capacity in various organs in the central nervous system, heart, kidneys, and liver makes it an intriguing model for studying inflammatory diseases. Regarding the zebrafish’s immune system, they possess analogous cells to neutrophils, macrophages, dendritic cells, B cells, and T cells found in mammals. Our laboratory investigates immune responses in inflammatory disease models in zebrafish as a tool to explore mechanisms for diseases and the actions of new therapeutic drugs.

In recent years, several national and international research groups, including ours, have consistently demonstrated the role of the inflammatory response in certain kidney diseases. Although advancements have been more prominent in animal models, the data generated strongly indicate that acute and chronic kidney injuries are influenced by the immune response, considered sterile, directed against compartments within the nephron. Now regarded as an epidemic, kidney diseases present a significant social and economic burden with high morbidity and mortality rates for patients. More recently, new molecules, hormones, and cellular subtypes have been identified and shown to participate in various inflammatory diseases. With lifestyle changes, new factors have been added to the list of kidney disease comorbidities, such as obesity. Alongside this, new hormones related to adipogenesis, alterations in intestinal microflora, fermentation products of these bacteria (short-chain fatty acids), and inflammatory molecules have emerged as playing roles in the pathogenesis of kidney injury.

Hematopoietic and non-hematopoietic stem cells, including mesenchymal stem cells, possess sufficient plasticity to regenerate tissues and restore physiological functions in damaged organs. Our laboratory investigates the immunological mechanisms involved in the trafficking of these cells into the kidney in models of acute and chronic kidney disease, their plasticity to differentiate into tubular cells, and their ability to modulate the inflammatory response in organ transplant models and acute renal injury.

Currently, induction of tolerance remains the sole strategy to increase graft survival without causing toxic damage to the graft. CD4+CD25+ T cells, or regulatory T cells, and NKT cells have been well characterized in the last decade, being described in humans in autoimmune diseases, viral infections, tumors, and organ transplantation. Our laboratory is interested in studying their frequency, cytokine production pattern, specificity, and trafficking in humans, primarily in kidney transplantation.