| Grant number: | 12/09611-0 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | September 01, 2012 |
| Effective date (End): | April 30, 2016 |
| Field of knowledge: | Biological Sciences - Morphology - Cytology and Cell Biology |
| Principal researcher: | Maria Cristina Roque Antunes Barreira |
| Grantee: | Thiago Aparecido da Silva |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract The lectin ArtinM, extracted from seeds of Artocarpus heterophyllus and characterized as a homotetramer consisted of is endowed with interesting biological properties: (1) it activates neutrophils through the recognition of N-glycans attached to CXCR2 and TLR2 receptors; (2) induces degranulation of mast cells by interacting with N-glycans of FcµR or to N-glycans of IgE bound to FcµR; (3) stimulates the production of IL-12 through the recognition of N-glycans of the TLR2 ectodomain, expressed on the surface of antigen presenting cells (APCs); (4) exerts immunomodulatory activity, which accounts for Th1 immunity (5) confers resistance to intracellular pathogens, such as P. brasiliensis, Leishmania amazonensis and Leishmania major, Neospora caninum e Candida albicans.CD4+ T cells participate in essential functions of the immune system can lead subpopulations cells suitable for generating efficient response to against pathogens, maintenance of tolerance and regulation of immunity. The effector function of CD8+ T cells (cytotoxic T lymphocyte, or CTL), in turn, is essential to control a variety of parasitic infections of intracellular pathogen. The cytotoxicity occurs by a mechanism involving the production of perforinas and granzymes, and the expression of FasL/CD95L membrane.This study is to analyze the effects of lectin ArtinM in CD4+ and CD8+ T cells murine, as for their differentiation and activation, as well as changes in their survival. There also, will be investigated the mechanisms responsible for the observed effects, which includes identifying glycotarget recognized by ArtinM and involved in signaling that triggers cellular response to stimulation with the lectin. This proposal is based on preliminary results indicate that ArtinM leads directly to activation of CD4+ T cell and induce to cytokine production by Th1 and Th17 profiles; these effects were display to be dependent on the recognition of glycans present in subunit ³ receptor CD3, involving signaling molecules PI3K PTK, p42/44MAPK, p38MAPK, JNK e PKC.The preliminary study will be investigated by evaluating the expression of costimulatory and inhibitory molecules, induction of cell differentiation and cell aggregation, cytokine production and cytotoxic activity; will also be expanded in order to assess the activation of CD8+ T cells. In addition, will investigate the survival of CD4+ and CD8+ T cells after stimulation with ArtinM, as well as identified signaling molecules related to this process. Finally, the glycans investigate constituents of the surface of CD4+ and CD8+ T cells involved in the specificity of ArtinM.Keywords: Lectins, ArtinM, CD4+ T cells and CD8+ T cells. | |