Translational evaluation of IgG effect upon the maturation of offspring thymus derived TCD4, TCD8, nTreg, gammadeltaT and e B cells.

• Grant number: 18/05181-7
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2019
• End date: August 31, 2021
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Alberto José da Silva Duarte
• Grantee: Alberto José da Silva Duarte
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 20/12929-8 - Translational evaluation of IgG effect upon the maturation of offspring thymic TCD4, TCD8, nTreg, gammadeltaT and B cells, BP.TT

Abstract

The regulation of children immunity mediated by maternal immune status as an immunomodulatory tool has been studied for decades in the literature. Among several evidences in this context, we have recently shown that pre-conception maternal immunization with the OVA allergen induces peripheral regulatory B cells (B10) in the murine offspring, and that this mechanism seems to be mediated by maternal IgG antibodies (De Oliveira et al., 2017 ). In a similar context, we have also recently shown that IgG antibodies purified from atopic individuals can modulate cytokine production by human intrathymic TCD4 and TCD8 cells (Sgnotto et al., 2017b; Sgnotto et al., 2018).Based on these recent results combined with other literature evidences, we recently proposed an unprecedented hypothesis, called MatIgG primary modulation theory (Victor, 2017), which will be elucidated with the execution of this proposal. The objective of this project is to use a murine model of maternal immunization with OVA allergen in which the effect of maternal IgG antibodies will be investigated upon the thymic maturation of TCD4, TCD8, nTreg, gammadeltaT and B cells that can exert regulatory and/or modulatory functions on offspring.This investigation also aim to investigate the effect of variations in the IgG repertoire and a translational approach will be performed using human thymic and peripheral cell that will be evaluated according to the results obtained in the murine model as well as in similar parameters.The results generated by this proposal are unpublished and will contribute to the development of regulatory immunologic therapies through the manipulation of the maternal immune system or directly by the passive transfer of IgG antibodies. Finally, this proposal will allow the training of students in different stages of scientific formation and the establishment of an international scientific collaboration. (AU)

Scientific publications

(15)

(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)

SANTOS, LUDIMILA S.; SGNOTTO, FABIO DA RESSUREICAO; SOUSA, THAMIRES R.; ORFALI, RAQUEL L.; AOKI, VALERIA; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON R.. IgG from atopic dermatitis patients induces non-atopic infant thymic invariant natural killer T (iNKT) cells to produce IL-4, IL-17, and IL-10. INTERNATIONAL JOURNAL OF DERMATOLOGY, OCT 2019. (18/05181-7)

VICTOR, JEFFERSON R.. Do different IgG repertoires play a role in B- and T-cell functional modulation during ontogeny? The ``hooks without bait{''} theory. Immunology and Cell Biology, v. 98, n. 7, APR 2020. (18/05181-7)

DE-OLIVEIRA, MARILIA G.; LIRA, ALINE A. L.; SGNOTTO, FABIO R.; INOUE, AMANDA H. S.; SANTOS, LUDIMILA S.; NAKAMATSU, BERNARDO Y.; DUARTE, ALBERTO J. S.; LEITE-DE-MORAES, MARIA; VICTOR, JEFFERSON R.. Maternal IgG impairs the maturation of offspring intrathymic IL-17-producing gamma delta T cells: Implications for murine and human allergies. CLINICAL AND EXPERIMENTAL ALLERGY, v. 49, n. 7, p. 1000-1012, JUL 2019. (17/18558-9, 18/05181-7)

DE-SOUSA, THAMIRES RODRIGUES; PESSOA, RODRIGO; NASCIMENTO, ANDREZZA; FAGUNDES, BEATRIZ OLIVEIRA; SGNOTTO, FABIO DA RESSUREICAO; DA SILVA DUARTE, ALBERTO JOSE; SANABANI, SABRI SAEED; VICTOR, JEFFERSON RUSSO. Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing gamma delta T Cells with Epigenetic Implications Mediated by microRNAs. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 12, JUN 2021. (18/05181-7, 18/08631-3)

DE SOUSA, T. R.; SGNOTTO, F. DA RESSUREICAO; FAGUNDES, B. OLIVEIRA; SANTOS, L. SOUZA; DA SILVA DUARTE, A. J.; VICTOR, J. R.. IgG from atopic individuals can mediate non-atopic infant thymic and adult peripheral CD8(+) TC2 skewing without influence on TC17 or TC22 cells. EUROPEAN ANNALS OF ALLERGY AND CLINICAL IMMUNOLOGY, v. 53, n. 4, p. 161-167, JUL 2021. (18/05181-7)

FAGUNDES, BEATRIZ OLIVEIRA; DE SOUSA, THAMIRES RODRIGUES; NASCIMENTO, ANDREZZA; FERNANDES, LORENA ABREU; SGNOTTO, FABIO DA RESSUREICAO; ORFALI, RAQUEL LEAO; AOKI, VALERIA; DUARTE, ALBERTO JOSE DA SILVA; SANABANI, SABRI SAEED; VICTOR, JEFFERSON RUSSO. IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma-Delta T Cells (gamma delta T) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 12, p. 16-pg., 2022-06-01. (18/05181-7, 18/08631-3, 19/09741-0)

DE SOUSA, THAMIRES RODRIGUES; FAGUNDES, BEATRIZ OLIVEIRA; NASCIMENTO, ANDREZZA; FERNANDES, LORENA ABREU; SGNOTTO, FABIO DA RESSUREICAO; ORFALI, RAQUEL LEAO; AOKI, VALERIA; DA SILVA DUARTE, ALBERTO JOSE; SANABANI, SABRI SAEED; VICTOR, JEFFERSON RUSSO. IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+T Cells: Possible Epigenetic Implications Mediated by miRNA. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 12, p. 18-pg., 2022-06-01. (18/08631-3, 19/09741-0, 18/05181-7)

SANTOS, LUDIMILA S.; SGNOTTO, FABIO DA RESSUREICAO; SOUSA, THAMIRES R.; ORFALI, RAQUEL L.; AOKI, VALERIA; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON R.. IgG from atopic dermatitis patients induces non-atopic infant thymic invariant natural killer T (iNKT) cells to produce IL-4, IL-17, and IL-10. INTERNATIONAL JOURNAL OF DERMATOLOGY, v. 59, n. 3, p. 6-pg., 2019-10-20. (18/05181-7)

SANTOS, LUDIMILA SOUZA; SGNOTTO, FABIO DA RESSUREICAO; SABO INOUE, AMANDA HARUMI; PADRECA, ARCHANGELO FERNANDES; MENGHINI, RICARDO PALAMAR; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON RUSSO. IgG from Non-atopic Individuals Induces In Vitro IFN-gamma and IL-10 Production by Human Intra-thymic gamma delta T Cells: A Comparison with Atopic IgG and IVIg. ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS, v. 67, n. 4, p. 263-270, AUG 2019. (18/05181-7)

DE OLIVEIRA, MARILIA GARCIA; SGNOTTO, FABIO DA RESSUREICAO; DE SOUSA, THAMIRES RODRIGUES; FAGUNDES, BEATRIZ OLIVEIRA; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON RUSSO. Preconceptional immunization with an allergen inhibits offspring thymic Th17 cells maturation without influence on Th1 and Th2 cells. EUROPEAN CYTOKINE NETWORK, v. 31, n. 3, p. 113-117, SEP 2020. (18/05181-7)

VICTOR, JEFFERSON R.. Do different IgG repertoires play a role in B- and T-cell functional modulation during ontogeny? The "hooks without bait" theory. Immunology and Cell Biology, v. 98, n. 7, p. 9-pg., 2020-04-28. (18/05181-7)

DE SOUSA, THAMIRES RODRIGUES; SGNOTTO, FABIO DA RESSUREICAO; FAGUNDES, BEATRIZ OLIVEIRA; DUARTE, ALBERTO JOSE DA SILVA; VICTOR, JEFFERSON RUSSO. Non-atopic Neonatal Thymic Innate Lymphoid Cell Subsets (ILC1, ILC2, and ILC3) Identification and the Modulatory Effect of IgG From Dermatophagoides Pteronyssinus (Derp)-Atopic Individuals. FRONTIERS IN ALLERGY, v. 2, p. 9-pg., 2021-04-28. (18/05181-7)

DE SOUSA, THAMIRES RODRIGUES; VICTOR, JEFFERSON RUSSO. Natural Self-Ligand Gamma Delta T Cell Receptors (gamma delta TCRs) Insight: The Potential of Induced IgG. VACCINES, v. 8, n. 3, SEP 2020. (19/09741-0, 18/05181-7)

INOUE, AMANDA HARUMI SABO; LIRA, ALINE APARECIDA DE LIMA; DE-OLIVEIRA, MARILIA GARCIA; DE SOUSA, THAMIRES RODRIGUES; SGNOTTO, FABIO DA RESSUREICAO; DUARTE, ALBERTO JOSE DA SILVA; VICTOR, JEFFERSON RUSSO. The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+B Cells (B10) Revealed in a Pilot Study. CELLS, v. 9, n. 10, OCT 2020. (18/05181-7)

SGNOTTO, FABIO DA RESSUREICAO; SANTOS, LUDIMILA SOUZA; DE SOUSA, THAMIRES RODRIGUES; DE LIMA, JOSENILSON FEITOSA; DA SILVA OLIVEIRA, LUANDA MARA; SANABANI, SABRI SAEED; DA SILVA DUARTE, ALBERTO JOSE; VICTOR, JEFFERSON RUSSO. IgG From HIV-1-Exposed Seronegative and HIV-1-Infected Subjects Differently Modulates IFN-gamma Production by Thymic T and B Cells. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v. 82, n. 5, p. E56-E60, DEC 15 2019. (18/05181-7)