Fig. 3: Development and downstream effectors of innate lymphoid cells, with particular attention given to ILC2s.

In adults, ILCs initially differentiate from common lymphoid progenitors (CLPs), which are commonly found in the bone marrow, via notch signaling. Transcription factors promote the differentiation of CLPs into ILC precursors (ILCPs), which further differentiate into NK cells, ILC1s, ILC3s, and ILC2s. Of interest, ILC2s express many surface receptors (e.g., IL7R, IL2R, IL33R, IL25R, IL4, IL4R, IL10R, and IL9R). Cytokines (dots) such as IL-5 and IL-13 are robustly produced by ILC2 stimulation and may activate microglial populations through pathways such as blood vessels or lymphatic drainage. Ultimately, ILC2 activation in disease may induce microglial activation and astrocyte activation, repress neuroinflammation and ameliorate cognitive deficits in an aging model.