The modulation of pulmonary group 2 innate lymphoid cell function in asthma: from inflammatory mediators to environmental and metabolic factors

A dysregulated type 2 immune response is one of the fundamental causes of allergic asthma. Although Th2 cells are undoubtedly central to the pathogenesis of allergic asthma, the discovery of group 2 innate lymphoid cells (ILC2s) has added another layer of complexity to the etiology of this chronic disease. Through their inherent innate type 2 responses, ILC2s not only contribute to the initiation of airway inflammation but also orchestrate the recruitment and activation of other members of innate and adaptive immunity, further amplifying the inflammatory response. Moreover, ILC2s exhibit substantial cytokine plasticity, as evidenced by their ability to produce type 1- or type 17-associated cytokines under appropriate conditions, underscoring their potential contribution to nonallergic, neutrophilic asthma. Thus, understanding the mechanisms of ILC2 functions is pertinent. In this review, we present an overview of the current knowledge on ILC2s in asthma and the regulatory factors that modulate lung ILC2 functions in various experimental mouse models of asthma and in humans. A subset of immune cells discovered in 2010 plays a prominent role in asthma, but the nature of their influence is unclear. T cells are the main drivers of the inflammatory response in asthma, but scientists have learned that another group of immune cells known as 'group 2 innate lymphoid cells' (ILC2s) also plays a role. Christina Li-Ping Thio and Ya-Jen Chang at the Academia Sinica, Taipei, Taiwan, have reviewed current knowledge of how ILC2s interact with other cells and tissues to influence asthma pathophysiology. Animal and human data strongly suggest that ILC2s help coordinate the immune response to allergen-induced asthma, although it remains unclear whether these cells are associated with more severe or treatment-resistant asthma. The authors highlight molecular signals that affect ILC2 function, including metabolic and dietary factors that could reduce asthma risk.

Automated summary

A dysregulated type 2 immune response is a key factor in the development of allergic asthma. In addition to Th2 cells, group 2 innate lymphoid cells (ILC2s) also play a role in the pathogenesis of this chronic disease. ILC2s not only contribute to the initiation of airway inflammation, but also interact with other immune cells to amplify the inflammatory response. Their ability to produce different types of cytokines further highlights their potential contribution to nonallergic, neutrophilic asthma.