Cariplo REMEDY Rif. 2019-3392 Peano Clelia (DSB.AD006.288)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute for Genetic and Biomedical Research (IRGB)

Project manager

CLELIA PEANO
Phone number: +393404775884
Email: clelia.peano@fht.org

Abstract

Restoration of relevant T cell functions may represent an exciting and innovative approach to the treatment
of this disorder. Based on preliminary data, this project will elucidate the miR-34 role in the SSRIs
mechanism of action and the interaction with the immune system. Through cutting-edge technologies we
will provide a new non-invasive tool to predict the individual susceptibility to SSRIs treatment and predispose
adequate strategies for therapeutic interventions. Our rationale stems from miR-34 mediated regulation of
the NF-ºB pathway that may be part of a mechanism acting partly independent of canonical NF-ºB signal
transduction and contributes to a modulation of T cell activity. Parallel to initiating the canonical NF-ºB
signalling cascade, T cell activation triggers an increase of miR-34 expression resulting in a "temporary T
cell inactivation" that may interrupt phases of T cell activity. We want to demonstrate an increase in
autoreactive T cells for central nervous system antigens, in peripheral blood of depressed patients based on
a deregulation of Treg activit

Goals

oReveal T cell diversity, V(D)J recombination, and immune cell profiling in peripheral blood to understand how the adaptive immunity is dynamically modulated in depression and in response to therapy.
oDescribe the miR-34 regulatory network, involved in the modulation of T cell activity, through total RNA sequencing and miRNA sequencing on T cells obtained from responding and non-responding- patients' blood samples
oGeneration of patient-specific human "disease-in-a-dish" model.
oValidation of human cerebral organoids to recapitulate cell architecture in mixed anxiety-depressive disorder.
oCharacterization of molecular and physical interaction between patient-specific cerebral organoids and circulating T cell subsets.
oRole of miR-34 in conditioning T cell subset differentiation and immune response.

Start date of activity

01/05/2020

Keywords

microRNA-34, Depression, Immunity

Last update: 23/04/2024