The role of invariant natural killer T cells in the development of glomerulonephritis: mechanisms and perspectives

• Grant number: 07/07120-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2008
• End date: June 30, 2012
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Alexandre de Castro Keller
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Alvaro Pacheco e Silva Filho ; Niels Olsen Saraiva Câmara ; Pamella Huey Mei Wang
• Associated scholarship(s): 11/06606-2 - The metabolism o endogenous glycolipids during the modulation of experimental glomerulonephritis by invariant Natural Killer T cells, BP.IC

Abstract

The invariant Natural Killer T cells (iNKT) are a distinct subpopulation of T lymphocytes. Recently, different studies showed that depending on the immunological context, the iNKT cells can play regulatory or effector role in the development of different pathologies. Preliminary results obtained during my Post-Doctoral stage at Necker Hospital- Paris, indicate that these cells exert a regulatory effect in the development of experimental anti-glomerular basement membrane glomerulonephritis. The glomerulonephritis are recognized worldwide as one of the most important cause of chronic renal insufficiency. These pathologies have a complex and unclear pathogenesis, thus its usual treatment is an immunosuppressive regimen. Therefore, the prognostics are frequently quite limited, resulting in a chronic disease which evolutes to fibrosis and lost of renal function. Hence, the development of alternative approaches in the treatment as well as new prognostics factors that can better characterize the evolution of these diseases is nowadays object of a great importance. The iNKT can promptly secret a large number of cytokines as IL-4, IFN-gamma, IL-10, IL-13 and others, playing an important role in the immune system homeostasis. Since my preliminary results pointed out an important role of the iNKT in the resistance to the development of anti-GBMGN, the aim of this project is to better understand its function in this disease and in another two GNs: the acute diffuse post-infectious GN and the IgA nephropathy. Moreover, this project will use experimental and clinical approach in order to adjoin basic science with medical experience allowing the evolution of the knowledge about this group of diseases and the improvement of researchers, physicians and students. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, RAFAEL L.; REIS, VANESSA O.; SEMEDO, PATRICIA; BUSCARIOLLO, BRUNA N.; DONIZETTI-OLIVEIRA, CASSIANO; CENEDEZE, MARCOS A.; SOARES, MARIA FERNANDA; PACHECO-SILVA, ALVARO; SAVAGE, PAUL B.; CAMARA, NIELS O. S.; et al. Invariant Natural Killer T Cell Agonist Modulates Experimental Focal and Segmental Glomerulosclerosis. PLoS One, v. 7, n. 3, MAR 12 2012. (07/07120-0)

MESNARD, LAURENT; KELLER, ALEXANDRE D. C.; MICHEL, MARIE-LAURE; VANDERMEERSCH, SOPHIE; RAFAT, CEDRIC; LETAVERNIER, EMMANUEL; TILLET, YVES; RONDEAU, ERIC; LEITE-DE-MORAES, MARIA C.. Invariant Natural Killer T Cells and TGF-beta Attenuate Anti-GBM Glomerulonephritis. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, v. 20, n. 6, p. 1282-1292, JUN 2009. (07/07120-0)

REIS, VANESSA OLIVEIRA; SILVA, JANICE COSTA; SOUZA, GABRIELA TRINDADE; SEMEDO, PATRICIA; BUSCARIOLLO, BRUNA; PEREIRA, RAFAEL LUIZ; CENEDEZE, MARCOS ANTONIO; PACHECO-SILVA, ALVARO; LONGO-MAUGERI, IEDA M.; SARAIVA CAMARA, NIELS OLSEN; et al. The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis. Immunobiology, v. 217, n. 9, p. 831-841, SEP 2012. (07/07120-0)

MESNARD, LAURENT; RAFAT, CEDRIC; VANDERMEERSCH, SOPHIE; HERTIG, ALEXANDRE; CATHELIN, DOMINIQUE; XU-DUBOIS, YI-CHUN; JOUANNEAU, CHANTAL; KELLER, ALEXANDRE CASTRO; RIBEIL, JEAN-ANTOINE; LEITE-DE-MORAES, MARIA C.; et al. Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis. FASEB JOURNAL, v. 25, n. 10, p. 3543-3553, OCT 2011. (07/07120-0)