The Hooks without bait theory: mechanisms involved in the immunomodulatory effect of IgG on the thymic modulation of TCD4, TCD8, gdT, iNKT MAIT and B cells, focus on atopic diseases and COVID-19

• Grant number: 21/08225-8
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: July 01, 2023
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Jefferson Russo Victor
• Grantee: Jefferson Russo Victor
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alberto José da Silva Duarte ; Maria Notomi Sato ; Sabri Saeed Mohammed Ahmed Al-Sanabani
• Associated scholarship(s): 23/16782-0 - Pilot study on cellular events involved in the immunomodulatory effect of murine IgG antibodies on thymic differentiation of TCD4, TCD8, gamma-deltaT, and B cells, BP.IC; 23/11315-4 - Elucidation of the cellular and molecular events involved in the immunomodulatory effect of IgG antibodies on the thymic differentiation of Tgd lymphocytes with a focus on atopic diseases and COVID-19, BP.MS; 23/11379-2 - Elucidation of cellular and molecular events involved in the effect immunomodulator of IgG antibodies on the thymic differentiation of TCD4 lymphocytes and TCD8 focusing on atopic diseases, BP.DD

Abstract

Although used for therapeutic purposes in various pathological processes with immunological etiology for many years, the precise mechanisms by which IgG antibodies can modulate immunity in the absence of antigen are not known, especially when considering their possible role in primary lymphoid organs such as the thymus. In recent years, several studies have shown that IgG can effectively play a modulatory role in lymphocyte differentiation in the thymus. This effect seems to be dependent on the idiotypic IgG repertoire, as it occurs in the absence of antigens and induces functional changes in several cell populations matured in the thymus, including several populations of human T and B lymphocytes. Based on the literature, especially on findings resulting from the therapeutic use of purified IgG (IVIg) and recent evidence obtained by our group, we have recently proposed the "hooks without bait" immunological theory. In this proposal, we aim to elucidate the cellular and molecular mechanisms involved in the aforementioned hypothesis to generate evidence that collaborates with the understanding of the mechanisms of thymic differentiation of TCD4, TCD8, gamma-deltaT, iNKT, MAIT, and B lymphocytes at the individual cellular transcriptional level as well as with the future development of therapies that use the transfer of IgG antibodies as a means of regulating human immunity. (AU)

Scientific publications

(4)

(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)

MACHADO, NICOLLE RAKANIDIS; FAGUNDES, BEATRIZ OLIVEIRA; FERNANDES, LORENA ABREU; DE OLIVEIRA, AUGUSTO CESAR PENALVA; NUKUI, YOUKO; CASSEB, JORGE; CUNHA, FERNANDO ROBERTO MACHADO; NALI, LUIZ HENRIQUE DA SILVA; SANABANI, SABRI SAEED; VICTOR, JEFFERSON RUSSO. Differential modulation of IL-4, IL-10, IL-17, and IFN-? production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and ?d) and B cells. FRONTIERS IN MEDICINE, v. 10, p. 8-pg., 2023-08-30. (21/08225-8)

CUNHA, FERNANDO ROBERTO MACHADO; FAGUNDES, BEATRIZ OLIVEIRA; MACHADO, NICOLLE RAKANIDIS; FRANCA, CAROLINA NUNES; VICTOR, JEFFERSON RUSSO. IgG from individuals without atopy arising as mediators of a nonatopic profile in human peripheral CD4+T cells. ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, v. 132, n. 6, p. 3-pg., 2024-06-03. (21/08225-8)

RECHE, DANIELA TERRA DE-APOENA; MACHADO, NICOLLE RAKANIDIS; FAGUNDES, BEATRIZ OLIVEIRA; BERGAMASCO, ISABELLA SIUFFI; DE SOUSA, THAMIRES RODRIGUES; DO NASCIMENTO, LAIS ALVES; CUNHA, FERNANDO ROBERTO MACHADO; DE-OLIVEIRA, MARILIA GARCIA; SGNOTTO, FABIO DA-RESSUREICAO; FRANCA, CAROLINA NUNES; et al. IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction. SCIENTIFIC REPORTS, v. 14, n. 1, p. 11-pg., 2024-03-27. (21/08225-8)

FERNANDES, LORENA ABREU; FOLGOSI, VICTOR ANGELO; PESSOA, RODRIGO; ASSONE, TATIANE; VICTOR, JEFFERSON RUSSO; CASSEB, JORGE; DE OLIVEIRA, AUGUSTO CESAR PENALVA; NUKUI, YOUKO; DUARTE, ALBERTO JOSE DA SILVA; SANABANI, SABRI SAEED. HTLV-1 and HTLV-2 infections significantly alter small RNA expression in asymptomatic carriers. FRONTIERS IN MEDICINE, v. 12, p. 13-pg., 2025-02-17. (22/09354-9, 21/08225-8)