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 Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: October 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Silvia Beatriz Boscardin
• Grantee: Silvia Beatriz Boscardin
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated 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)

Scientific publications

(8)

(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)

SOUZA, HIGO FERNANDO SANTOS; ZANETI, ARTHUR BARUEL; ALMEIDA, BIANCA DA SILVA; MARTINHO, JESSICA AMARAL; YAMAMOTO, MARCIO MASSAO; ROSA, DANIELA SANTORO; SLHESSARENKO, RENATA DENZEGRINI; BOSCARDIN, SILVIA BEATRIZ. Reactivity of DENV-positive sera against recombinant envelope proteins produced in bacteria and eukaryotic cells. IMMUNOLOGIC RESEARCH, v. 71, n. 1, p. 12-pg., 2022-10-03. (17/26342-6, 18/07142-9)

SILVA, MARIANGELA O.; ALMEIDA, BIANCA S.; SALES, NATIELY S.; DINIZ, MARIANA O.; APS, LUANA R. M. M.; RODRIGUES, KARINE B.; SILVA, JAMILE R.; MORENO, ANA C. R.; PORCHIA, BRUNA F. M. M.; SULCZEWSKI, FERNANDO B.; et al. Antigen Delivery to DEC205(+) Dendritic Cells Induces Immunological Memory and Protective Therapeutic Effects against HPV-Associated Tumors at Different Anatomical Sites. International Journal of Biological Sciences, v. 17, n. 11, p. 2944-2956, 2021. (18/26515-0, 18/07629-5, 15/16505-0, 16/00708-1, 18/07142-9)

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)

FERREIRA, NATALIA S.; LIMA, NATHALIA F.; SULCZEWSKI, FERNANDO B.; SOARES, IRENE S.; FERREIRA, MARCELO U.; BOSCARDIN, SILVIA B.. Plasmodium vivax infection changes the peripheral immunoregulatory network: CD4 T follicular cells and B cells. European Journal of Immunology, v. N/A, p. 15-pg., 2023-05-24. (18/07142-9, 16/18740-9, 16/50108-0)

ANDREATA-SANTOS, ROBERT; MACHADO, RAFAEL RAHAL GUARAGNA; DOS SANTOS ALVES, RUBENS PRINCE; SALES, NATIELY SILVA; SOARES, CAMILA PEREIRA; RODRIGUES, KARINE BITENCOURT; SILVA, MARIANGELA OLIVEIRA; FAVARO, MARIANNA TEIXEIRA DE PINHO; RODRIGUES-JESUS, MONICA JOSIANE; YAMAMOTO, MARCIO MASSAO; et al. Validation of Serological Methods for COVID-19 and Retrospective Screening of Health Employees and Visitors to the Sao Paulo University Hospital, Brazil. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 8-pg., 2022-06-02. (20/08943-5, 16/20045-7, 21/05661-1, 14/50890-5, 16/23560-0, 15/02352-7, 20/06409-1, 17/24769-2, 16/14344-1, 18/23680-0, 20/10700-3, 18/07629-5, 18/07142-9)

BOSCARDIN, SILVIA BEATRIZ. Antigen targeting to dendritic cells as a way to improve vaccine design. European Journal of Immunology, v. 51, p. 1-pg., 2021-08-01. (18/07142-9)

BOSCARDIN, SILVIA BEATRIZ; DUDZIAK, DIANA; MUENZ, CHRISTIAN; ROSA, DANIELA SANTORO. Editorial: Harnessing the Participation of Dendritic Cells in Immunity and Tolerance. FRONTIERS IN IMMUNOLOGY, v. 11, p. 4-pg., 2020-10-07. (18/07142-9, 17/17471-7)