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"Mechanisms involved on offspring allergy development regulation by maternal immunization: role of cytokines, induction of T and B regulatory cells and allergen nature."

Grant number: 15/17256-3
Support type:Regular Research Grants
Duration: February 01, 2016 - July 31, 2018
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Alberto José da Silva Duarte
Grantee:Alberto José da Silva Duarte
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Jefferson Russo Victor


Abstract: Over the last 13 years our research group has been studying the effects of maternal immunization with allergens such as the dust mite Dermatophagoides pteronyssinus (Der p) and Ovalbumin (OVA) in regulating offspring allergic response (FUSARO AE et al, 2002 , VICTOR JR et al, 2003 FUSARO AE et al 2007, FUSARO AE et al, 2009). At this time, our results indicate that maternal immunization with OVA is capable of modulating the phenotype of offspring B and dendritic cells (VICTOR JR et al, 2010, MUNIZ BP et al, 2014), apparently through a different mechanism compared with maternal immunization with Der p (LIRA AAL et al, 2014).Based on this evidence, it is likely that the maternal immunization is capable of induce or modulate populations of T and B cells with regulatory or modulatory functions in the progeny, and that the induction of these populations can be influenced by allergen structural nature. Thus, this project aims the continuity of our research line on the investigation of regulatory mechanisms of offspring allergic response mediated by maternal immunization with emphasis on cytokine production and induction of lymphocyte with regulatory and/or modulatory functions on the offspring.In the cytokines modulation context, our previous results showed influence of maternal immunization on offspring IL-4, IL-10, IL-12 and IFN-g production. To elucidate the importance of these cytokines we will use genetically deficient mice (KO) of each and observe its importance in the studied mechanism.In the regulatory population context, we will investigate the induction of the main populations of regulatory and/or modulatoty cells described in the literature. Among them, the Th17 cells, T regulatory cells (Treg: CD4+ CD25+ Foxp3+ and Tr1) and B regulatory cells (Breg: B10, Br17 and CD19highFcgRIIbhigh) that can participate in the regulation of offspring allergic response and where not yet elucidated. The participation of Treg cells has been suggested by our group (VICTOR et al, 2003 Muniz BP et al, 2014) but not evidenced in vivo. The participation of Th17, Tr1, B10, Br17 and B CD19highFcgRIIbhigh cells where unprecedented.Finally, it will be carried out maternal and neonatal immunization protocol with an allergen that can induce type I hypersensitivity responses in humans, the dust mite Der p for the evaluation of the specificity and to approach our results to evidences in humans.The results from this proposal will collaborate with the clarification of mechanisms involved in the inhibition of offspring allergic response by maternal immunization and therefore to improve future maternal vaccination strategies with allergens for newborns protection. (AU)

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Scientific publications (6)
(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)
DE LIMA LIRA, ALINE APARECIDA; DE-OLIVEIRA, MARILIA GARCIA; SABO INOUE, AMANDA HARUMI; BELTRAME, GIOVANNA ROSSI; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON RUSSO. Preconceptional allergen immunization can induce offspring IL-17 secreting B cells (B17): do they share similarities with regulatory B10 cells?. ALLERGOLOGIA ET IMMUNOPATHOLOGIA, v. 46, n. 5, p. 454-459, SEP-OCT 2018. Web of Science Citations: 5.
SGNOTTO, FABIO D. R.; DE OLIVEIRA, MARILIA G.; LIRA, ALINE A. L.; INOUE, AMANDA H. S.; TITZ, TIAGO O.; ORFALI, RAQUEL L.; BENTO-DE-SOUZA, LUCIANA; SATO, MARIA N.; AOKI, VALERIA; DUARTE, ALBERTO J. S.; VICTOR, JEFFERSON R. IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant intrathymic TCD4 and TCD8 cells. INTERNATIONAL JOURNAL OF DERMATOLOGY, v. 57, n. 4, p. 434-440, APR 2018. Web of Science Citations: 5.
DE OLIVEIRA, MARILIA GARCIA; DE LIMA LIRA, ALINE APARECIDA; SGNOTTO, FABIO DA RESSUREICAO; SABO INOUE, AMANDA HARUMI; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON RUSSO. Preconception immunization can modulate intracellular Th2 cytokine profile in offspring: in vivo influence of interleukin 10 and B/T cell collaboration. CENTRAL EUROPEAN JOURNAL OF IMMUNOLOGY, v. 43, n. 4, p. 378-388, 2018. Web of Science Citations: 1.
DE OLIVEIRA, MARLIA GARCIA; OLIVEIRA, LUANA DE MENDONCA; DE LIMA LIRA, ALINE APARECIDA; SGNOTTO, FABIO DA RESSUREICAO; DA SILVA DUARTE, ALBERTO JOSE; SATO, MARIA NOTOMI; VICTOR, JEFFERSON RUSSO. Preconception allergen sensitization can induce B10 cells in offspring: a potential main role for maternal IgG. ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY, v. 13, APR 17 2017. Web of Science Citations: 7.
DA RESSUREICAO SGNOTTO, FABIO; GARCIA DE OLIVEIRA, MARILIA; DE LIMA LIRA, ALINE APARECIDA; BENTO-DE-SOUZA, LUCIANA; DA SILVA DUARTE, ALBERTO JOSE; RUSSO VICTOR, JEFFERSON. Low doses of IgG from atopic individuals can modulate in vitro IFN-gamma production by human intra-thymic TCD4 and TCD8 cells: An IVIg comparative approach. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 13, n. 7, p. 1563-1572, 2017. Web of Science Citations: 5.
VICTOR, JEFFERSON RUSSO. Allergen-specific IgG as a mediator of allergy inhibition: Lessons from mother to child. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 13, n. 3, p. 507-513, 2017. Web of Science Citations: 8.

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