Therapeutic Potential of Group 2 Innate Lymphoid Cells in Neuroinflammatory Diseases

Group 2 innate lymphoid cells (ILC2s) are tissue-resident immune cells that regulate type 2 immunity, neuroimmune communication, inflammation resolution and tissue repair. Although ILC2s are best characterized in peripheral barrier tissues, increasing evidence indicates that they also participate in central nervous system (CNS) immunity. In the healthy adult CNS, ILC2s are mainly located in border compartments such as the meninges and choroid plexus, while they are rare in brain parenchyma. After CNS injury, however, ILC2s can expand or infiltrate injured tissues and contribute to immune regulation, angiogenesis and neurorepair. This review summarizes peripheral ILC2 features most relevant to neuroinflammatory therapy, including neuropeptide responsiveness, reparative functions and maladaptive remodelling risks. We then discuss ILC2 distribution and function in the dura/meninges, choroid plexus and injured brain parenchyma. Recent studies reveal that CNS-associated ILC2s regulate microglia/macrophages through IL-4 and IL-13, recruit eosinophils through IL-5, promote post-stroke angiogenic initiation through α-CGRP, and support neural stem/progenitor cell-mediated repair through amphiregulin. We further discuss therapeutic opportunities and challenges, including targeted homing, stage-dependent repair effects, ILC2 plasticity and ex vivo expansion for cell therapy. These findings position ILC2s as multifunctional neuroimmune effectors with potential therapeutic value in neuroinflammatory diseases.