USE OF TIM-3 INHIBITORS FOR THE TREATMENT OF EXACERBATIONS IN PATIENTS SUFFERING FROM SEVERE ASTHMA

摘要

Rhinovirus infections are the main cause of asthma exacerbations. As Natural Killer (NK) cells are important actors of the antiviral innate response, the inventors aimed to evaluate the functions of NK cells from severe asthmatic patients in response to rhinovirus or rhinovirus-like molecules. Peripheral blood mononuclear cells from severe asthmatic patients and healthy donors were stimulated with pathogen-like molecules or with the human rhinovirus A9 (HRV). NK cell activation, degranulation and IFN-γ expression were analyzed. The inventors found NK cells from severe asthmatic patients were less cytotoxic and expressed less IFN-γ than NK cells from healthy donors. NK cells from severe asthmatics exhibited an exhausted phenotype, with an increased expression of Tim-3. Finally, the inventors show that neutralization of Tim3 restores rhinovirus-induced NK cell activation. Together, the findings prompt to consider that Tim-3 inhibitors would be suitable for treating exacerbation in patients suffering from severe asthma.