Role of miRNAs in regulatory T cell-mediated immunological tolerance

• Grant number: 16/13029-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2016
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Flavia Franco da Cunha
• Supervisor: Li-Fan Lu
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 14/07390-1 - Mesenchymal stromal cells derived microvesicles as inductors of immune tolerance, BP.DR

Abstract

Regulatory T (Treg) cells play an important role in maintaining immune homeostasis and the balance between immunity and tolerance. Expression of Foxp3 is essential for the differentiation and function of Treg cells as ablation or mutation of this transcription factor results in the development of severe autoimmune diseases in mice and in humans. Recent studies demonstrated that microRNAs (miRNAs) are also critical for Treg cell homeostasis and suppressor function. Mice knocked out for Dicer or Drosha (two enzymes essential for miRNA biogenesis) in Foxp3+ cells harbor impaired Treg cell populations, which leads to a fatal systemic autoimmune disease similar to that was observed in mice without Treg cells. Among the miRNAs that are differentially expressed in Treg cells, the family of miR-23-27-24 is of particular interest. While their role in immune regulation remains not well established, recently it was shown that mice with T cell-specific miR-23 cluster ablation developed Th2-associated immunopathology during airway allergic reaction. On the other hand, the role of this cluster in regulating Treg cells has not been demonstrated yet. In this application, we hypothesize that the absence of this miRNA family in Treg cells will impact their suppressor function leading to unbalanced immune responses. By using the loss-of-function genetic approaches, we will directly assess the role of miR-23 clusters in controlling Treg cell biology.

Scientific publications

(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)

DA CUNHA, FLAVIA FRANCO; ANDRADE-OLIVEIRA, VINICIUS; DE ALMEIDA, DANILO CANDIDO; DA SILVA, TAMIRIS BORGES; DE SOUZA BREDA, CRISTIANE NAFFAH; CRUZ, MARIO COSTA; FAQUIM-MAURO, ELIANA L.; CENEDEZE, MARCOS ANTONIO; HIYANE, MEIRE IOSHIE; PACHECO-SILVA, ALVARO; et al. Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4(+) T Lymphocytes Toward a Regulatory Profile. CELLS, v. 9, n. 4, APR 2020. (17/05264-7, 18/08479-7, 14/07390-1, 16/13029-5)