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Influence of the STAT5 signaling pathway in conventional dendritic cells on the instruction of helper T cell response

Grant number: 22/00204-4
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2022
Effective date (End): December 31, 2026
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Silvia Beatriz Boscardin
Grantee:Guilherme Antonio de Souza Silva
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Splenic conventional Dendritic Cells (cDCs) are central in the process of inducing the immune response, as they are capable of presenting antigens from different pathogens and inducing the activation of naive T cells. In mice, splenic cDCs are often classified into cDC1 (expressing the alpha chain of the CD8 molecule and the endocytic receptor DEC205, CD8±+DEC205+) and into cDC2 (CD8± negative and expressing the endocytic receptor DCIR2, CD8±-DCIR2+). The cDC1 subtype can recognize intracellular pathogens and initiate a majority production of IL-12, polarizing CD4+ T cells to a predominantly Th1 profile. The cDC2 subtype is related to the polarization of CD4+ T cells for the establishment of a Th2 profile against parasites and a Th17 profile in response to extracellular bacteria. Furthermore, cDC2s can induce TFH cells that activate B lymphocytes to produce high titers of antibodies. In recent years, our group has been working to try to understand the biology of these cells, especially regarding the signaling pathways that could be involved in the induction of such polarizations. In this context, signal transducer and transcription activator proteins (STATs) play an important role in the differentiation of these cDCs, since they are involved in the transmission of signals from extracellular molecules and establish a transcriptional regulatory mechanism. Thus, the present project aims to evaluate the role of the STAT5 signaling pathway in DEC205+CD8±+ and DCIR2+CD8±- cDCs, analyzing the ability of each subtype to instruct the T helper response. For the proposed purpose, we intend to use mice that do not express STAT5 specifically in cDCs (STAT5 cKO). Splenic cDCs from these animals will be isolated and analyzed in vitro for their ability to present antigens to CD4+ T cells, as well as their subsequent polarization to Th1, Th2, Th17, TFH and TReg profiles. To specifically study the influence of STAT5 on the instruction of CD4+ T cells in vivo, the antigen targeting strategy for CD8±+ cDCs via DEC205 receptor and for CD8±- via DCIR2 receptor will be used. (AU)

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