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

• Grant number: 18/00145-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2018
• Effective date (End): August 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Silvia Beatriz Boscardin
• Grantee: Fernando Bandeira Sulczewski
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

There are mainly two Dendritic Cell (DC) subtypes in the murine spleen, one expressing the endocytic receptor CD205 (DEC205) and the alpha chain of CD8 molecule (DEC205+CD8±+) and another express the endocytic receptor DCIR2, but not expressed the CD8± molecule (DCIR2+CD8±-). The CD8±+ DC is mainly responsible for antigen cross-presentation to prime CD4+ and CD8+ T cells. On the other hand, the CD8±- subtype is associated with CD4+ T cells priming. Recently, using an antigen targeting to DC strategy, we have identified that CD8±+ and CD8±- DCs promote distinct CD4+ T cell polarization. CD8±+ DCs primed Th1 cells and CD8±+ DCs primed TFH cells. In this project, we are planning to study in more details the DCs subsets capacity to prime T cells, evaluating the role of STAT1, STAT3, STAT5 and STAT6 signaling pathways in CD8±+ and CD8±- DCs, in order to study the ability of each subtype to prime T helper response. For this, we intend to use mice in which the STAT 1, 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 Th1, Th2, Th17, TFH and TReg polarization will be analyzed in vitro. To study the influence of STAT pathways on CD4+ T cell priming by both DC subtypes in vivo, we will use the antigen targeting strategy to access CD8±+ DCs via the DEC205 and CD8±- receptor via the DCIR2 receptors. We hope to contribute to the understanding of mechanisms related to the specialization of each DC subsets to prime CD4+ T cell response. (AU)

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)

SULCZEWSKI, FERNANDO BANDEIRA; MARTINO, LARISSA ALVES; ALMEIDA, BIANCA DA SILVA; ZANETI, ARTHUR BARUEL; FERREIRA, NATALIA SOARES; DA SILVA AMORIM, KELLY NAZARE; YAMAMOTO, MARCIO MASSAO; APOSTOLICO, JULIANA DE SOUZA; ROSA, DANIELA SANTORO; BOSCARDIN, SILVIA BEATRIZ. Conventional type 1 dendritic cells induce T(H)1, T(H)1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor. European Journal of Immunology, v. 50, n. 12, JUL 2020. (18/20821-2, 15/18874-2, 17/06503-5, 15/16565-2, 18/00145-2, 18/07142-9)

DE SOUZA-SILVA, GUILHERME ANTONIO; SULCZEWSKI, FERNANDO BANDEIRA; BOSCARDIN, SILVIA BEATRIZ. Recombinant antigen delivery to dendritic cells as a way to improve vaccine design. Experimental Biology and Medicine, v. N/A, p. 8-pg., 2023-09-25. (22/00204-4, 18/00145-2)

SULCZEWSKI, FERNANDO BANDEIRA; MARTINO, LARISSA ALVES; SALLES, DAVI; YAMAMOTO, MARCIO MASSAO; ROSA, DANIELA SANTORO; BOSCARDIN, SILVIA BEATRIZ. STAT3 signaling modulates the immune response induced after antigen targeting to conventional type 1 dendritic cells through the DEC205 receptor. FRONTIERS IN IMMUNOLOGY, v. 13, p. 15-pg., 2022-10-18. (18/20821-2, 18/00145-2, 14/50890-5, 17/17471-7, 18/07142-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SULCZEWSKI, Fernando Bandeira. Influence of STAT3 and STAT6 Signaling Pathways in Conventional Type 1 and 2 Dendritic Cells to Prime Auxiliary T Cell Responses.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.