PhD Scientific Days 2020

Molecular Sciences I. Lectures

The Mammalian Target of Rapamycin Regulates the Rig-I-Like Receptor-Mediated Immun Functions in Human Dendritic Cells

Előadó neve

Ágics, Beatrix, MSc

Előadó munkahelye

Department of Immunology, Faculty of Medicine, University of Debrecen, Doctoral School of Molecular Cellular and Immune Biology

Előadó telefonszáma

+36 52 411 717 /65104

Előadó e-mail címe

agics.beatrix@med.unideb.hu

Az előadás címe

The Mammalian Target of Rapamycin Regulates the Rig-I-Like Receptor-Mediated Immun Functions in Human Dendritic Cells

Szerző(k) neve és munkahelye

Beatrix Ágics1,2, Tünde Fekete1, Kitti Pázmándi1
1Department of Immunology, Faculty of Medicine, University of Debrecen, 2Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen

Szekció

Molecular Sciences I. Lectures

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction:As professional antigen-presenting cells, dendritic cells (DC) provide an essential link between innate and adaptive immunity. The unique feature allows DCs to deliver antigens into the lymphoid tissues where they interact with naive T cells and initiate their activation, expansion and differentiation. DC functions are tightly regulated by the mammalian target of rapamycin (mTOR) that controls numerous cellular processes of DCs including metabolism, transcriptional responses, development, maturation, cytokine production, and T cell stimulatory activity. Previously mTOR was identified as a critical regulator of Toll-like receptor-dependent DC activation, however the role of mTOR in the regulation of RIG-I-like receptor (RLR)-mediated DC functions has not been explored yet.
Aim:Our goal is to study the possible modulatory effects of mTOR on the outcomes of RLR-mediated immune responses in human DCs.
Methods:Human monocyte-derived DCs were pre-treated with mTORC1 inhibitor, rapamycin at therapeutically achievable concentrations then activated with specific RLR ligands. Changes in RLR-mediated responses of DCs were monitored by Q-PCR, flow cytometry, ELISA, lactate-assay and western blotting, whereas their T-cell activating capacity was examined by CFSE assay and intracellular flow cytometry after co-culturing with naïve CD8+T cells.
Results:We found that mTOR inhibition did not induce remarkable changes in RLR-mediated expression of cell surface molecules, however significantly decreased the RLR-induced pro-inflammatory and polarizing cytokine secretion of DCs. Furthermore, mTOR blockade impaired the activation-induced glycolytic transition in the cells and diminished the ability of RLR-stimulated DCs to promote the proliferation of IFN-γ producing CD8+T cells.
Conclusion:Our results demonstrate that the regulatory function of mTOR is also essential to elicit RLR-induced activation, cytokine production and T cell stimulation of human DCs providing additional insight into the complexity of mTOR-mediated DC functions.
Funding:NKFIH FK 128294,EFOP-3.6.3-VEKOP-16-2017-00009 and GINOP-2.3.2-15-2016-00050 projects,UNKP-19-4 New National Excellence Program of the Ministry for Innovation and Technology managed by the National Research,Development and Innovation Office and the János Bolyai Research Scholarship from the Hungarian Academy of Sciences.

Additional Information

Kitti Linda Pázmándi
pazmandi.kitti@med.unideb.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4625

Start

10:20

End

10:35

Authors (legacy)

Beatrix Ágics1,2, Tünde Fekete1, Kitti Pázmándi1
1Department of Immunology, Faculty of Medicine, University of Debrecen, 2Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen