mRNAs, miRNAs and Regulatory Molecules Expression profile in the Immune Response in Renal Allograft

• Grant number: 10/14946-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2011
• Effective date (End): May 31, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Antônio Donadi
• Grantee: Daiani Cristina Cilião Alves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Renal transplantation is the treatment of choice for patients with end-stage renal disease. The induction of tolerance is the primary aim in organ transplantation, and success for the acceptance of allogenic transplantation is dependent on the interaction of several genetic and immunological mechanisms. The transcriptional profile observed in renal allograft and peripheral blood lymphocytes, using microarrays, has been used to identify genes modulated in various stages of transplantation, and found hundreds of genes involved in the rejection. miRNAs have a variety of tasks, highlighting the modulation of expression of several proteins by degrading or preventing the translation of mRNAs, being several of them involved in allograft rejection. In addition to the differential transcriptional analysis, several genes are potentially involved in the mechanisms of tolerance. The molecule HLA-G is reported as a modulator of extracellular signaling by interacting with inhibitory receptors found on immune cells. Regulatory T cells (Treg) from CD4+ CD25+, actively suppress the immune response against self antigens, alloantigens and tumor antigens, promoting tolerance antigen-specific suppression of activation and expansion of effectors cells, and the transcription factor Foxp3 marker as well characterization of this lineage. The PD-1 and CTLA-4 are members of the CD28 receptor family. The CTLA-4 acts as an inhibitor of T-cell activation and PD-1 also has an inhibitory function on T cells and B cells, being important in peripheral tolerance. The IL-17, secreted by Th17 cells, can stimulate macrophages, stromal cells and activate epithelial cells of renal tubules to secrete proinflammatory cytokines. Galectins are a family of proteins that bind to carbohydrates on the surface of cells, regulating the amount of leukocytes through of apoptotic and non-apoptotic mechanisms being galectin-3 the most well studied of these lectins. Whereas there are no studies evaluating both the transcriptional profiles (mRNA and miRNA) in renal allografts and that there are few studies of the immune regulatory molecules in renal allografts, this study proposes to investigate the interaction of transcriptional profiles in renal allografts, presenting or not rejection, and also the protein expression of several molecules involved in the modulation of the immune response (HLA-G, Foxp3, PD1, CTLA-4, IL-17 and Gal 3), correlating with the mechanisms of rejection. Them, we will perform microarray of microRNAs and mRNAs and immunohistochemistry for the regulatory molecules in renal allografts with or without rejection (acute and chronic). Understanding the mechanisms that contribute to the rejection of the allograft may contribute to the development of anti-rejection strategies.

Scientific publications

(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)

CILIAO ALVES, DAIANI CRISTINA; DE OLIVEIRA CRISPIM, JANAINA CRISTIANA; CASTELLI, ERICK C.; MENDES-JUNIOR, CELSO TEIXEIRA; SALOUN DEGHAIDE, NEIFI HASSAN; BARROS SILVA, GYL EANES; COSTA, ROBERTO SILVA; SABER, LUCIANA TANAJURA; MOREAU, PHILIPPE; DONADI, EDUARDO ANTONIO. Human leukocyte antigen-G 3 ` untranslated region polymorphisms are associated with better kidney allograft acceptance. HUMAN IMMUNOLOGY, v. 73, n. 1, p. 52-59, JAN 2012. (10/14946-5)

CILIAO ALVES, DAIANI CRISTINA; DE OLIVEIRA CRISPIM, JANAINA CRISTIANA; CASTELLI, ERICK C.; MENDES-JUNIOR, CELSO TEIXEIRA; SALOUN DEGHAIDE, NEIFI HASSAN; BARROS SILVA, GYL EANES; COSTA, ROBERTO SILVA; SABER, LUCIANA TANAJURA; MOREAU, PHILIPPE; DONADI, EDUARDO ANTONIO. Human leukocyte antigen-G 3 ' untranslated region polymorphisms are associated with better kidney allograft acceptance. HUMAN IMMUNOLOGY, v. 73, n. 1, p. 8-pg., 2012-01-01. (10/14946-5)