LYRA_2015-0010 FRRB - Analisi a singola cellula di linfociti che infiltrano siti della autoimmunità: dissezione dei meccanismi immunologici dell'artrite reumatoide (DSB.AD008.355)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of biomedical technologies (ITB)

Project manager

GIANLUCA DEBELLIS
Phone number: 0226422700
Email: gianluca.debellis@cnr.it

Abstract

Cellular complexity within the immune system is critical for the generation of the different effector responses required to protect the host against a broad range of threats. Emerging single-cell technologies, provide unprecedented opportunities to draw a accurate picture of immune cells functions, including basic mechanisms of response, transitions from normal to disease states and response to therapies becoming also the basis for "precision medicine". Rheumatoid Arthritis (RA) is a devastating autoimmune disease characterised by chronic destructive synovitis leading to joint deformities and disability. RA has been intensely investigated, yet, several critical issues remain to be addressed: i. its pathobiology is multifaceted and not yet completely understood and implicates local inflammatory response linked to altered intestinal flora; ii. the lack of specific and sensitive biomarkers represents a major unmet medical need; iii. there are available therapeutic options which show some efficacy; however, the discovery of novel targets could also lead to the development of improved medical treatments with higher efficacy and specificity and reduced side effects.

Goals

This project aims at addressing these issues by developing a platform for single cell transcriptomic, multicolor flow-cytometry and advanced in vivo imaging analysis of immune cells isolated from both peripheral blood and disease sites of RA patients and pre-clinical models. The single cell platform will be integrated with the epigenetic and whole transcriptomic analysis from the immune cells isolated from the same sites of RA patients, together with the microbiome analysis. These studies will be performed also on a unique cohort of "treatment naïve" RA patients at the initial stage of the disease. The relevance of our findings will be thus greatly enhanced by the lack of other co-factors (e.g ongoing or previous treatments, disease stage) that might otherwise undermine the validity of the results. Overall, we expect that this multidisciplinary approach will define suitable strategies to unveil cell-type specific molecular processes and pathways underlying not only the pathogenesis of RA but, more in general, autoimmune diseases, whose findings can be effectively translated to advance clinical practices

Start date of activity

01/01/2017

Keywords

single cell analysis, rheumatoid arthritis, genomics

Last update: 01/06/2024