Searching for the Elusive Regulatory Innate Lymphoid Cell

The complex nature of the innate lymphoid cell (ILC) family and wide range of ILC effector functions has been the focus of intense research. In addition to important roles in host defense, ILCs have central roles in maintaining tissue homeostasis and can promote immune tolerance. Alterations within the microenvironment can impart new functions on ILCs, and can even induce conversion to a distinct ILC family member. Complicating current definitions of ILCs are recent findings of distinct regulatory ILC populations that limit inflammatory responses or recruit other immunosuppressive cells such as regulatory T cells. Whether these populations are distinct ILC family members or rather canonical ILCs that exhibit immunoregulatory functions due to microenvironment signals has been the subject of much debate. In this review, we highlight studies identifying regulatory populations of ILCs that span regulatory NK-like cells, regulatory ILCs, and IL-10-producing ILC2s.