Effect of histamine on the activation of dendritic cells and CD4+T cells mediated by the agonists of toll-like receptors in the newborn

• Grant number: 12/16524-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2012
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Notomi Sato
• Grantee: Maria Notomi Sato
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Cyro Alves de Brito

Abstract

Histamine is a biogenic amine with a broad action on several cell types including those which perform relevant immune functions. It is able to polarize some effector functions such as type 2 dendritic cells and to promote Th2 response by distinct intracellular signals. The blockade of histamine receptors associated with adjuvant may enhance the immune response. Adjuvants like the synthetic Toll-like receptors (TLRs) ligands have been widely investigated by its immunomodulatory potential. In the neonatal period, there is a sub-optimal activation of IL-12/IFN-g axis, resulting in an inadequate activation of dendritic cells and Th1 function, which emphasizes the search for strategies to enhance the immune response. The goal of this Project is to analyze the effect of histamine on dendritic cells and CD4+ T cells from newborns (human umbilical cord) compared to the adults. Moreover, we aim to evaluate the modulatory potential of histamine receptor antagonists as well as the TLRs agonists. The effect of histamine and receptors (H1R-H4R) will be evaluate in the pro inflammatory cytokines and chemokines secretion induced by agonists TLR4, TLR7 / 8, TLR9 in mononuclear cells from the umbilical cord blood and adults. The action of histamine and receptor H4R will be analyzed in monocyte-derived dendritic cells activated by agonists of TLR4 and TLR7/8 in the secretion of cytokines, molecules expression, AP1 and NF-kB signaling pathway and in the generation of heterologous T cells secreting IL-4 or IFN-g. Moreover, the modulatory potential of histamine and receptors H4R will be assessed in CD4+ T cells polarized in the Th1/Th2 though cytokine secretion profile, expression of histaminic receptors and genes related with Th1/Th2 function by PCR array. The search for strategies to enhance the immune response may contribute to understanding the neonatal immunology and to develop new vaccine formulations. (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)

CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; YAMADA YOSHIKAWA, FABIO SEITI; PIETROBON, ANNA JULIA; SATO, MARIA NOTOMI. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators of Inflammation, 2018. (12/16524-6)

CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; PEREIRA, NATALLI ZANETE; YAMADA YOSHIKAWA, FABIO SEITI; DA SILVA OLIVEIRA, LUANDA MARA; EMIDIO TEIXEIRA, FRANCIANE MOURADIAN; OLIVEIRA, LUANA DE MENDONCA; PIETROBON, ANNA JULIA; TORREALBA, MARINA PASSOS; DE LIMA, JOSENILSON FEITOSA; DA SILVA DUARTE, ALBERTO JOSE; et al. Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine. SCIENTIFIC REPORTS, v. 9, SEP 23 2019. (16/24680-9, 12/16524-6)

CALVIELLI CASTELO BRANCO, ANNA CLAUDIA; YAMADA YOSHIKAWA, FABIO SEITI; PIETROBON, ANNA JULIA; SATO, MARIA NOTOMI. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators of Inflammation, v. 2018, p. 10-pg., 2018-01-01. (12/16524-6)