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Analysis of interleucin 10 influence in cellular and humoral responses promoted by antigen targeting to the CD8a+DEC205+ dendritic cells

Grant number: 18/20821-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2019
Effective date (End): December 31, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Silvia Beatriz Boscardin
Grantee:Larissa Alves Martino
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Conventional dendritic cells (cDCs) are antigen-presenting cells capable of instructing the adaptive immune response and influencing the polarization of CD4 + T cells. According to the expression of different surface markers, cDCs can be divided into two basic subtypes: CD8a+DEC205+ and CD8a-DCIR2+. Previous results from our laboratory indicate that CD8a+DEC205+ cDCs are able to instruct CD4+ T cells with polarization to the Th1 profile, and also IL-10 producing CD4+ T cells. It is known that IL-10 is a cytokine that has anti-inflammatory abilities, acting in the regulation and suppression of the expression of pro-inflammatory cytokines. However, little is known about the role of IL-10 in promoting the immune response induced in vaccination protocols that target antigens to CD8a+DEC205+ cDCs. In this sense, we intend to use an antigen targeting model for CD8a+DEC205+ cDCs which consists in the use of a chimeric monoclonal antibody (mAb) (anti-DEC205) fused to a protein of interest (ovalbumin) to send it directly to these cells. This strategy has been widely used for the study of cellular and humoral immune responses, including as a vaccine strategy for the induction of protective immune responses against different pathogens. Thus, we intend to analyze the effects promoted by IL-10 in the context of antigen targeting to CD8±+DEC205+ cDCs using C57BL/6 IL-10 knockouts (IL-10 KO) and C57BL/6 wild-type (WT) mice. For this, we will carry out immunizations using the anti-DEC205 mAb fused to the protein ovalbumin (aDEC-OVA) and a mAb consisting of isotype control (ISO-OVA) in the presence of the poly (I: C) adjuvant. After the second dose, the Th1 CD4+ T cell response, the germinal center cells formation and the humoral response will be analyzed in the spleen and in the sera of the mice. We also intend to analyze the influence of IL-10 on the protective immune response induced by antigen targeting to CD8a+DEC205+ cDCs after the challenge of WT and IL-10 KO mice with B16F0-OVA melanoma cells. Thus, we hope to elucidate in more detail some of the effects of IL-10 on the immune response promoted by antigen targeting to CD8a+DEC205+ cDCs.

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. Web of Science Citations: 1.

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