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Influence of STAT1, STAT3, STAT5 and STAT6 signaling pathways on conventional dendritic cells in the instruction of the T-cell auxiliary response

Grant number: 18/07142-9
Support type:Regular Research Grants
Duration: May 01, 2019 - April 30, 2021
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Silvia Beatriz Boscardin
Grantee:Silvia Beatriz Boscardin
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Daniela Santoro Rosa

Abstract

In the mouse spleen, there are mainly two subtypes of dendritic cells (DCs), one expressing the endocytic receptor CD205 (DEC205) and the alpha chain of the CD8 receptor (DEC205+CD8±+), and another expressing the DCIR2 endocytic receptor, but not the the CD8± molecule (DCIR2+CD8±-). The DEC205+CD8±+ subtype has the ability to instruct CD4+ T lymphocytes, and to cross-present extracellular antigens to instruct CD8+ T lymphocytes. On the other hand, the DCIR2+CD8±- DC subtype is associated with the instruction of CD4+ T cells. Recently, by targeting one antigen to each DC subtype using hybrid monoclonal antibodies against the receptors DEC205 or DCIR2, we have identified that these DC subtypes induce distinct polarizations of helper CD4+ T cells. In this project, we intend to expand our studies and evaluate the role of the signaling pathways of STAT1, STAT3, STAT5 and STAT6 in DEC205+CD8±+ and DCIR2+CD8±- DCs, in order to study the ability of each subtype to instruct the T cell helper response. For this purpose, we intend to use mice in which the STAT1, STAT3 and STAT5 molecules will be specifically deleted in DCs and STAT6 knockout mice. The spleen DCs from these animals will be isolated and their ability to present antigens to CD4+ T cells, as well as their instruction to Th1, Th2, Th17, TFH and TReg profiles will be analyzed in vitro. To study the influence of STAT pathways on CD4+ T cell instruction by both DC subtypes in vivo, we will use the antigen targeting strategy for CD8±+ DCs via the DEC205 and CD8±- receptor via the DCIR2 receptor. We hope to contribute to the understanding of mechanisms related to the specialization of each DC subtype in instructing a CD4+ T cell response. (AU)