RIISPAD

Role of innate immunity in the pathogenesis of autoimmune diseases

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 Obiettivo del progetto (Objective)

'We propose a multidisciplinary “translational research” project that will exploit the molecular and cellular features of innate immunity potentially involved in the pathogenesis of autoimmune diseases in humans. Given the significant scientific advances over the past years in characterizing the physiology of cells from the innate immune system, we will attempt to identify the role of natural killer (NK) cells and dendritic cells (DCs) in the physiopathology of various autoimmune disorders. Combining different professional expertise in clinical and basic immunology, we plan the following: 1) To select cohorts of patients affected by several systemic autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (scleroderma) and other various forms of vasculitis. We will conduct our investigations on both naive untreated patients with active disease and patients undergoing immuno-suppressive therapy with disease in remission, in either cross-sectional or longitudinal studies 2) To collect total peripheral blood lymphocytes through either blood draws or leukapheresis procedures in order to obtain large numbers of cells for analysis. 3) To identify significant aberrancies in the phenotype and functions of NK cells and DCs that may further our understanding of the physiopathology of autoimmunity. 4) To better understand how innate and adaptive immunity are linked and whether aberrant interactions between the two arms of the immune system lead to the lack of immunological tolerance in autoimmune disorders, in order to develop alternative therapeutic approaches to autoimmune disorders 5) To develop new diagnostic tools that better characterize the status of innate immune competent cells and improve classification of the stages of autoimmune disorders, which could lead to a more effective use of immunosuppressive agents.'

Introduzione (Teaser)

Scientific advances make it possible to characterise the physiology of cells taken from the innate immune system. This is important for the study of autoimmune diseases.

Descrizione progetto (Article)

This multidisciplinary translational research project is working to identify the role of natural killer (NK) cells and dendritic cells (DCs) in the pathogenesis of human autoimmune disorders. Achieving its objectives will help the development of innovative therapeutic approaches and more efficient diagnostic tools. And being able to improve classification of the stages of autoimmune disorders could lead to more effective use of immunosuppressive agents.

The 'Role of innate immunity in the pathogenesis of autoimmune diseases' (Riispad) project divided its original experimental plan into two distinct projects. First, researchers are looking into how NK cells are implicated in autoimmune diseases, the aim being to analyse whether they have any role in the physiopathology of autoimmune disorders. Since there is evidence to associate some autoimmune diseases and the development of lymphomas, the project also intends to investigate the ability of NK cells to clear tumour target cells.

In the first two years, Riispad received ethical approval from the Institutional Review Board. The team recruited patients, set up a clinical database, developed new experimental data and sought more financial support. In fact, the Italian Association for Cancer Research has awarded the Riispad project a three-year Investigator Grant.

In the second project, researchers are examining NK cells and autoimmune arthritis. Their main aim is to identify novel NK cell biomarkers to enable early diagnosis and clinical follow-up as physicians are often hard-pressed to identify the nature of arthritis in its early stages. Project partners also looked for additional financial support for this study and have been awarded a two-year grant by the Intramural research Program of Istituto Clinico Humanitas.