IL-7: The global builder of the innate lymphoid network and beyond, one niche at a time

The development and homeostasis of adaptive and innate lymphocytes is dependent on the stromal cytokine IL-7. The initial priming of immune responses to pathogenic challenges is executed by innate lymphoid cells (ILCs) with programmed capacity to rapidly secrete effector cytokines. How ILCs are controlled by IL-7 in distinct anatomical locale has evolved into a more complex problem as IL-7 receptor is not only expressed on ILCs, but also on surrounding neighbors, including vascular endothelium and mesenchymal cells that compete for limiting IL-7. For the generation of γδ T and B cells IL-7 is required for the production of antigen receptors, and it is likely that IL-7 performs critical function in facilitating ILC effector programming in addition to its regulatory actions on cell survival and proliferation. Most of our current understanding of the highly calibrated regulatory circuits of IL-7 function and IL-7 receptor signaling has derived from studies of adaptive, conventional lymphocytes. Here we highlight recent advances in mapping the gene circuits and cellular interactions that regulate temporospatial activities of IL-7 in diverse macro and micro niches that have direct relevance to deciphering the sphere of impact of IL-7 on ILC differentiation.

► We discuss newly emerging details on the regulation of IL-7R expression.
► IL-7 regulates the differentiation of all innate lymphoid cells in diverse tissues.
► IL-7 may be a permissive factor for arming innate effectors.
► Complex competition for IL-7 by multiple cell types in a given niche is addressed.