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The role of reduced folate carrier (SLC19a1) on the differentiation, stability and function of regulatory T lymphocytes

Grant number: 20/04170-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Biological Sciences - Pharmacology
Principal researcher:José Carlos Farias Alves Filho
Grantee:Gabriel Azevedo Públio
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

Regulatory T cells are key players on the maintenance of immunologic homeostasis, as they are capable of negatively regulate the immune response. However, it is not yet fully elucidated what are the necessary signals for regulatory T cell activation on the inflammatory site. The intracellular protein STING ("STimulator of Interferons Genes"), it's a receptor that recognizes cyclic dinucleotides on the cytoplasm and has been the focus of study on many innate immune cells' responses. These cyclic dinucleotides were initially identified on viruses and bacteria, been with the immune response that produces type I Interferons. Despite this protein been express in lymphocytes, little is known about its role in these cells' functions. Unpublished data of our research group showed that the activation of lymphocytes with cyclic dinucleotides induces higher expression of the transcriptional factor Foxp3, when cultivated in a Treg polarization condition, suggesting that the activation of STING regulates positively the differentiation to Tregs. Recently, it was demonstrated that the entry of cyclic dinucleotides on macrophages its mediated by SL19a1, which was initially described as the reduced folate carrier. Therefore, we hypothesize that this transporter must be express by Tregs, which facilitates the entry of cyclic dinucleotides present on the inflammatory sites, and that is an important signal for the differentiation and activation of Tregs. In fact, preliminary data of this project shows that the genic expression of SLC19a1 is higher on Treg cells when compared to other lymphocytes subpopulation, however, its importance in the function and differentiation on lymphocytes remains unknown. Thus, this project has as its main goal to evaluate the role of SLC19a1 in the capture of cyclic dinucleotides and its impact on Treg cells differentiation and function. (AU)

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