Asthma is an inflammatory disorder that was once treated as a single disease. Conventional asthma treatment involves the use of inhaled glucocorticosteroids and bronchodilators (e.g. β2-adrenergic agonists) to inhibit inflammation and airway constriction. However approximately 20% of asthma patients are poorly responsive to steroid treatment and have increased risk of hospitalization and death. Respiratory infections are thought to be one of the major risk factors that trigger the steroid resistant exacerbations. In these patients innate inflammatory mediators and cells are linked to pathogenesis and disease severity. Our investigations have identified novel roles of interleukin (IL)-36 family cytokines in regulating airway inflammation and alterations in lung function during infection and pathogen-induced exacerbation of asthma. We found that the expression of IL-36γ was significantly increased by pathogen-associated molecular patterns derived from bacteria and viruses in macrophages. Administration of recombinant IL-36γ, in vitro (bronchial epithelial cells) and in vivo (lungs), increased TNF-α, IL-1β, IL-6, IL-33, IL-13, and CXCL1 expression. Interestingly, treatment with IL-36γ also increased recruitment of both type 2 innate lymphoid cells (ILC2) and dendritic cells (DC), both are critical for asthma pathogenesis. We next sought to determine the importance of IL-36γ in asthma using a well-characterised murine model of allergic airway disease. Mice were sensitised and challenged with ovalbumin (OVA) to induce hallmark features of asthma. During allergen challenge, recombinant IL-36γ was administered intranasally and pulmonary function was assessed. Mice treated with IL-36γ became insensitive to corticosteroid therapy. In conclusion, we show that infections that trigger asthma exacerbations are linked to IL-36 production and that delivery of this cytokine to the airways results in steroid-resistant airway hyperresponsiveness and neutrophilic inflammation. Our results suggest that IL-36γ could be a potential therapeutic target for neutrophilic and severe asthmatics.