Group 2 Innate Lymphoid Cells and Cytotoxic T cells in Type-2 Inflammatory Diseases: Outsiders inside out

Asthma is a chronic inflammatory disease of the airways, characterized by reversible airway obstruction associated with chest tightness and shortness of breath. The current standard treatment for asthma patients includes anti-inflammatory corticosteroids, which have proven effective for many patients. However, a subset of patients does not adequately respond and present themselves with a form of corticosteroid-insensitive disease that is generally accompanied with frequent exacerbations. A primary goal of current asthma research is to better understand the underlying causes of therapy-resistance and exacerbations, and to ultimately provide better treatment options to the group of severe asthma patients. This thesis focused on addressing these central issues by investigating two specific cell types that have received less attention in the field: group 2 innate lymphoid cells (ILC2) and CD8+ cytotoxic T cells (Tc). As these cells are known to have the capacity to produce type-2 cytokines, we hypothesized that they may be important players in asthma pathogenesis.
The results presented in this thesis provide compelling evidence for an important contribution of ILC2s and Tc cells in severe type-2 immunopathologies, as well as a plausible explanation for resistance to corticosteroids in asthma. Further investigations into the mechanisms that drive the activation of these cells could lead to new strategies for treating patients with severe therapy-resistant chronic airway inflammation. Moreover, transcriptome profiles of immune cells acquired upon steroid and/or vitamin D treatment could significantly contribute in the discovery of new factors associated with steroid resistance or in the ongoing pursuit of identifying novel biomarkers.