Multifaceted roles of interleukin-7 signaling for the development and function of innate lymphoid cells

Recently, additional innate lymphocyte subsets have been identified that express germline encoded immunoreceptors and respond to cytokine cues. Among these, innate lymphoid cells (ILC) at mucosal surfaces are of significant interest because they were found to play important roles for lymphoid organogenesis, tissue homeostasis and repair, for immunity to various infections but also have been involved as disease-promoting cells in models of chronic inflammatory diseases and of autoimmunity. Their functional and transcriptional programs strikingly resemble that of the various T helper cell subsets suggesting that these programs are already pre-formed in the innate immune system and that these may be more conserved than previously appreciated. Interestingly, all ILC subsets express the interleukin 7 receptor α chain and IL-7 signaling has been involved in various aspects of their developmental and functional programs. Here, we will review the role of IL-7 signaling for the differentiation, maintenance and function of two important ILC subsets, lymphoid tissue inducer cells (i.e., RORγt+ ILC) and natural helper cells (i.e., type 2 ILC). We will also put emphasis on the recently discovered role of IL-7 in controlling plasticity of RORγt+ ILC.

► Role of IL-7 signaling for lymphoid organogenesis.
► Role of the aryl hydrocarbon receptor in regulating IL-7 receptor expression.
► IL-7 and the regulation of RORγt+ ILC cell fate decisions.
► IL-7 controls plasticity of RORγt+ ILC.