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Characterization of TGF-b signaling in the chronic graft-versus-host disease after allogeneic bone marrow transplant

Grant number: 15/16758-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2016
Effective date (End): January 31, 2017
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Patricia Maria Bergamo Favaro
Grantee:Beatriz Corey Morini
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Nowadays, allogeneic hematopoietic cell transplantation is the cure for several patients with benign and malignant hematologic diseases. Many complications can occur after bone marrow transplant and the Graft-versus-host disease (GVHD) is one of the most important due to mortality and impact on quality of life. Approximately 50% of patients have some manifestation of chronic GVHD, although the pathophysiology of GVHD is not yet fully understood. There is evidence that immune tolerance to self antigens would be broken in chronic GVHD, giving rise to autoimmune manifestations. In this context, the regulatory T cells (Tregs) are important, since the suppression of alloreactive T effector cells by Treg cells is an important mechanism involved in the balance between graft rejection versus tolerance to the graft. There are indications that the Treg suppression is mediated by cytokines such as TGF-b, which can act on the control of proliferation and differentiation of T cells and inducing the expansion of Treg cells. Therefore, it is possible that the path of TGF-b has a role in chronic GVHD. Both microRNA (miRNA) -155 and the miRNA146a have been related to the route of TGF- b. Thus, the aim of this project, the characterization of the expression of major elements of the pathway of TGF-b as well as the expression of miR-155 and miR-146a in mononuclear cells from peripheral blood of patients with GVHD.