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

• Grant number: 23/11315-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2023
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Jefferson Russo Victor
• Grantee: Nicolle Rakanidis Machado
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/08225-8 - 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, AP.JP

Abstract

Among the evidence that gave rise to the hypothesis of this project, it has been demonstrated that the IgG from atopic (allergic) individuals is capable of inhibiting thymic maturation of IFN-³-producing CD4 T lymphocytes, which play an inhibitory role in the development of allergies (1). In the same context, it has been shown that IgG from atopic individuals can promote the maturation of IL-4-producing CD8 T lymphocytes that may contribute to the development of allergies (2). In the context of ³´ T lymphocytes, a recent study has shown that IgG from tolerant individuals is able to inhibit thymic maturation of IL-17-producing ³´ T lymphocytes in vitro (3). Furthermore, concerning ³´ T lymphocytes, it has been demonstrated that purified IgG from allergen-tolerant individuals is capable of promoting the production of cytokines related to the inhibition of allergy development by ³´ T lymphocytes, namely IFN-³ and IL-10 (4). Additional approaches have also encompassed populations of less frequent lymphocytes in the thymus. It has been shown that purified IgG from patients with atopic dermatitis is capable of inducing the production of IL-17, IL-10, and IL-4 by thymic iNKT lymphocytes, which may participate in the pathogenesis of chronic inflammatory dermatological disease (5), and that IgG from atopic individuals can promote the maturation of type 2 innate lymphoid cells (ILC2s) as well as the production of IL-13, both factors related to allergy development (6). Not limited to atopic diseases, some studies have also shown the effect of IgG repertoires in the context of infectious diseases. In this regard, a recent study has demonstrated that purified IgG from HIV-1-infected patients or individuals exposed but not infected by this virus can differentially influence the production of IFN-³ by human thymic CD4, CD8, ³´ T lymphocytes, and B lymphocytes (7). In addition to the need to investigate the immunomodulatory mechanisms mediated by different IgG antibody repertoires, there is also a need to select appropriate immunological contexts that justify and position the execution of this master's degree in the current scientific state of the art. In the meantime, the focus of the proposal on COVID-19 has been determined due to its responsibility for the current pandemic state, having accumulated over 170 million confirmed cases and nearly 4 million deaths since its characterization in December 2019 (8). Finally, we emphasize that, due to the approval of the research proposal in the Young Researcher line, in which this scholarship was granted as a budgetary item, we foresee the incorporation of other dermatological or infectious pathologies to strengthen the potential for nucleation of group activities.