Innate Lymphoid Cells: Novel Effectors of Immune Defense and Tissue Homeostasis

Innate lymphoid cells (ILC) are a newly described family of hematopoietic cells that lack antigen-specific receptors but can be activated to promptly produce large amounts of cytokines (including interleukin (IL)-5, -13, -17A, -22, TNF- and interferon-γ) and thereby contribute to the immediate, first-line immune defense against viral, bacterial, and parasitic infections. ILCs include the previously described natural killer (NK) cells and have a similar 'natural' effector function which is immediately available during immune responses and prior to that of adaptive immunity. Three groups of ILC (ILC1, ILC2, ILC3) have been described that share biological activities of T helper (Th)1, Th2 and Th17/22 subsets and CTL. ILCs are active during both fetal and adult life and play important roles in the homeostasis of mucosal and non-mucosal tissues. How ILCs develop from hematopoietic precursors is poorly defined and how ILCs are integrated into ongoing immune responses remains unclear. Knowledge in this arena is a prerequisite for harnessing the clinical potential of these potent immune effector cells. My laboratory investigates the critical control points that regulate ILCs differentiation and plasticity. Using complementary approaches, we hope to shed new light on the biological determinants which condition ILC reactivity in mice and man. Understanding how the threshold of ILC responsiveness is set prior to and during immune responses may have important implications for disease intervention.