UC San Diego

Allergic asthma is characterized by airway inflammation, hyperresponsiveness, and remodeling. Group 2 Innate Lymphoid cells (ILC2s) are a relatively newly discovered cell type that likely contributes to the pathogenesis of asthma. ILC2s produce type 2 cytokines IL-5 and IL-13, which leads to the development of the allergic asthma phenotype that includes tissue eosinophilia and mucus production. ILC2s belong to a class of immune cells collectively known as innate lymphocytes (ILCs), and recent literature has shown that plasticity occurs between the ILC subtypes under specific conditions. Our studies demonstrate that IL-18 may control the plasticity of ILC2s in vivo through modulation of cytokine production. IL-18R-/- mice, which lack the IL-18 receptor, demonstrated an enhanced asthma phenotype that was characterized by an increase in lung and BAL eosinophils. The ILC2s in the IL-18R-/- mice displayed unconventional cytokine production and were found to more actively produce the ILC3 cytokine IL-17A. Further studies into the plasticity of ILC2s may lead to the discovery of new treatments for asthma by controlling the activity of ILC2s by taking advantage of their plasticity.