Abstract
Innate lymphoid cells (ILCs) are tissue resident cells that are triggered through a relatively broad spectrum of alarmins, inflammatory cues, neuropeptides, and hormones. Functionally, ILCs are akin to subsets of helper T cells and are characterized by a similar effector cytokine profile. They also share a dependency on many of the same essential transcription factors identified for the maintenance and survival of T cells. The key distinguishing factor between the ILC family and T cells is the lack of antigen-specific T cell receptor (TCR) on ILCs and, thus, they can be considered the "ultimate invariant T cells". ILCs, like T cells, orchestrate downstream effector inflammatory responses by adjusting the cytokine microenvironment in a fashion that promotes protection, health, and homeostasis at mucosal barrier sites. But also, like T cells, ILCs have recently been implicated in several pathological inflammatory disease states. This review focuses on the selective role of ILCs in the development of allergic airway inflammation (AAI) and fibrosis in the gut where a complex ILC interplay has been shown to either attenuate or worsen disease. Finally, we discuss new data on TCR gene rearrangements in subsets of ILCs that challenge the current dogma linking their origin to committed bone marrow progenitors and instead propose a thymic origin for at least some ILCs. In addition, we highlight how naturally occurring TCR rearrangements and the expression of major histocompatibility (MHC) molecules in ILCs provide a useful natural barcode for these cells and may prove instrumental in studying their origins and plasticity.