Regulation of the adaptive immune system by innate lymphoid cells

• Innate lymphoid cells (ILCs) are critical regulators of immune responses in lymphoid and barrier tissues.
• ILCs modulate adaptive immune cell responses indirectly through cytokine-mediated regulation of stromal cells and epithelial cells.
• ILCs can also directly regulate adaptive immune cells via MHCII or other cell-surface bound molecules.
• ILC regulation of adaptive immune cells may be of clinical relevance in a wide range of chronic human inflammatory diseases.

Innate lymphoid cells (ILCs) are a group of lymphocytes that promote rapid cytokine-dependent innate immunity, inflammation and tissue repair. In addition, a growing body of evidence suggests ILCs can influence adaptive immune cell responses. During fetal development a subset of ILCs orchestrate the generation and maturation of secondary lymphoid tissues. Following birth, ILCs continue to modulate adaptive immune cell responses indirectly through interactions with stromal cells in lymphoid tissues and epithelial cells at barrier surfaces. In this review we summarize the current understanding of how ILCs modulate the magnitude and quality of adaptive immune cell responses, and in particular focus on recent evidence suggesting that ILCs can also directly regulate CD4+ T cells. Further, we discuss the implications that these pathways may have on human health and disease.