A three course menu for ILC and bystander T cell activation

The varied list of agonists that activate innate lymphoid cells (ILCs) continues to grow, but whether and how these signals interact is not well defined, especially in vivo. ILC subsets share master transcription factors, chromatin landscapes, and effector cytokines with their corresponding T helper (Th) cell subsets. Here we discuss how studies of these two cell types can inform each other. Specifically, we outline a framework in which ILC agonists are grouped by the transcription factors they activate. Optimal ILC activation requires at least three items from a 'menu' of non-redundant signals that collectively replicate the STAT and TCR signaling that drives effector Th cell function. This conceptual model may also apply to TCR-independent 'bystander' activation of Th cells.