NILTHERA

Novel Interleukins for immunotherapy of Asthma

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Allergies are increasing in incidence at an alarming rate. One in three Europeans suffers from an allergy and one in ten children suffers from asthma. From the E.U. perspective, the cost from allergies in terms of health care and absenteeism from work is estimated at 45 billion euros a year. Despite prioritization of allergies and asthma in recent E.U. Framework Programme activities, there are major gaps of knowledge in this area that hamper the design of new therapeutic strategies. Recently, a new family of cytokines termed lambda IFNs, Type III IFNs or IL-28/29 (IFNλ/IL-28s) was described. IFNλ/IL-28s signal though a unique receptor complex (IL-28Rα/IL 10R2) and possess antiviral and antitumour activity. However, their role in adaptive immunity and allergic diseases has not been explored. This is despite two reports linking the levels of expression of IFNλ/IL-28s with reduced severity of asthma in humans. The host laboratory has therefore initiated a study to investigate the role of IFNλ/IL-28s in allergic asthma and found that IFNλ/IL-28s possess potent immunomodulatory activity that suppresses allergic airway disease in mice. The primary objective of this proposal is to further explore this observation through (i) the in-depth investigation of the role of IFNλ/IL-28s in allergic airway disease, (ii) the unwinding of the cellular and molecular events involved, (iii) and the development of novel immunotherapeutic approaches for the treatment of allergic asthma. The secondary objective is to support reintegration and career development of the Marie Curie fellow by expanding her training to chronic inflammatory disease pathogenesis and to new technologies and interdisciplinary skills. The high quality research environment of the Host Organization, the international collaborations of the host laboratory which is a partner and coordinator of other FP7 Actions and the innovative and translational nature of the project guarantee the success of both aims of the proposal.'

Introduzione (Teaser)

A European study investigated the role of an immune regulator molecule in allergic asthma and defined its impact at the cellular and molecular levels. The NILTHERA project outcome could contribute towards the development of novel immunotherapeutic approaches for the treatment of allergic asthma.

Descrizione progetto (Article)

Asthma is an allergic respiratory disease, affecting over 30 million European citizens. Although disease symptoms and severity vary, the overall health care costs mount to billions of euros per year. Additional costs to the European economy also accrue due to loss of productivity and absenteeism from work.

The aim of the EU-funded 'Novel Interleukins for immunotherapy of asthma' (NILTHERA) was to evaluate the role of interleukins-28/29 in the development of allergic airway inflammation. Project scientists used mice that had a deletion in the IL-28 receptor and studied the effect of endogenous signalling on T cell differentiation. IL-28 cytokines proved to be critical for driving cytotoxic CD8+ T cell differentiation in the expense of CD4+ effector T cells.

As a result, IL-28R knockout mice developed allergic airway inflammation and hyper-responsiveness to allergens associated with increased CD4+ T cell responses. Also, when scientists treated wild-type mice with IL-28 cytokine, they observed a suppression of CD4+ T cells and a reduction of respiratory inflammation.

The effect of IL-28 on T cells was found to be mediated through dendritic cells, the professional antigen-presenting cells of the immune system. In their attempt to delineate the underlying mechanism of IL-28 activity, researchers discovered that IL-28 affected a number of molecular pathways that determine dendritic cell function.

In order to study the biology of IL-28 cytokines in vivo and map where and when they are being expressed, NILTHERA scientists generated a transgenic mouse model where IL-28 fluoresced. This model has great potential for screening existing and novel agonists of IL-28 as treatment for asthma.

Taken together, the results of the NILTHERA study indicate that treatment with IL-28 could alleviate the symptoms of asthma, thereby improving the quality of life of asthma sufferers.