The metabolism o endogenous glycolipids during the modulation of experimental glomerulonephritis by invariant Natural Killer T cells

• Grant number: 11/06606-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2011
• End date: May 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Nathália Amato Khaled
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 07/07120-0 - The role of invariant natural killer T cells in the development of glomerulonephritis: mechanisms and perspectives, AP.JP

Abstract

The invariant Natural Killer T cells (NKT) are a distinct subpopulation of T lymphocytes that have as major characteristics the selectivity for glycosphingolipids (GSL) conjugated with the CD1d molecule and the rapid secretion of a large number of cytokines upon TCR activation. Because the NKT cells secrete both pro and anti-inflammatory cytokines, different works associated these lymphocytes with the induction or modulation of diverse diseases induced by immune responses.Recently, Prof. Keller et al., demonstrated that NKT cells have a renoprotective role in the experimental mode of anti-glomerular basal membrane glomerulonephritis (anti-GBMGN) (JASN, 2009). Because the activation of NKT cells is mainly dependent of GSL recognition, the first objective of this project is to detect alterations in the metabolism of glycolipids during the development of anti-GBMGN. Thereby, we can determine the class of the endogenous GSL that is associated with the renoprotective effect of NKT cells. In parallel, we will study the effect of NKT activation by pro-Th1 or pro-Th2 agonists on the development of anti-GBMGN.Our preliminary results demonstrate that the pro-Th1 agonist GSL-1 can protect from anti-GBM development in comparison to those that have pro-Th2 properties (OCH, PBS-27 and PBS-120). The next question is to determine the mechanisms involved in the renoprotective effect of GSL-1 and if during this process the metabolism of endogenous NKT agonists as GM3, GD3 and iGb3 is affected.The present project is part of a research field that is well established in the laboratory of Prof. Keller and will be supported by the grants from the Project nº 2007/07120-0 (Jovem Pesquisador). This line of research will contribute to the understanding of the inflammatory process involved in the development of glomerulonephritis and constitute an important support for the training of Nathália Amato Khaled, an I.C. student.