Group 3 Innate Lymphoid Cells: A Potential Therapeutic Target for Steroid Resistant Asthma

Asthma is a chronic airway inflammatory disease that affects millions globally. Although glucocorticoids are a mainstay of asthma treatment, a subset of patients show resistance to these therapies, resulting in poor disease control and increased morbidity. The complex mechanisms underlying steroid-resistant asthma (SRA) involve Th1 and Th17 lymphocyte activity, neutrophil recruitment, and NLRP3 inflammasome activation. Recent studies provided evidence that innate lymphoid cells type 3 (ILC3s) might be potential therapeutic targets for non-eosinophilic asthma (NEA) and SRA. Like Th17 cells, ILC3s play crucial roles in immune responses, inflammation, and tissue homeostasis, contributing to disease severity and corticosteroid resistance in NEA. Biologics targeting ILC3-related pathways have shown promise in managing Th2-low asthma, suggesting new avenues for SRA treatment. This review aims to explore the risk factors for SRA, discuss the challenges and mechanisms underlying SRA, consolidate current findings on innate lymphoid cells, and elucidate their role in respiratory conditions. We present the latest findings on the involvement of ILC3s in human diseases and explore their potential mechanisms in SRA development. Furthermore, we review emerging therapeutic biologics targeting ILC3-related pathways in managing NEA and SRA. This review highlights current challenges, and emerging therapeutic strategies, and addresses a significant gap in asthma research, with implications for improving the management of steroid-resistant asthma.