Intrathymic IL-7: The where, when, and why of IL-7 signaling during T cell development

The thymus is the birthplace of all T lineage cells. But the thymus is also a cradle as it provides the environment for further maturation and differentiation of immature thymocytes. While many factors contribute to make the thymus a unique place for T cell development, here we review the essential role of intrathymic interleukin-7 (IL-7). In the absence of IL-7 signaling, survival, proliferation and differentiation of immature thymocytes are all severely impaired. Consequently, IL-7 is critical to nurture and guide T precursor cells through the diverse steps of thymic maturation. Interestingly, even as IL-7 signaling is such a critical factor, IL-7 signaling must be also actively suppressed during specific stages of T cell differentiation. These contradictory observations are puzzling but can be satisfactorily explained when understanding the developmental context of IL-7 signaling. In this regard, here we will discuss the spatiotemporal expression of intrathymic IL-7 and address the stage-specific effects of IL-7 signaling in developing thymocytes. Specifically, we will review other facets of intrathymic IL-7 beyond its role as a pro-survival factor and so clarify and reaffirm the unique role of IL-7 as a prime factor in T cell development and differentiation.

► Immature thymocytes require IL-7 signaling for survival, proliferation, and differentiation. ► IL-7 is produced by thymic stromal cells but not by thymocytes themselves. ► Desensitization to IL-7 is also critical for thymocyte development. ► Positive selection and CD4 lineage commitment are proposed to be induced in IL-7 refractory cells. ► Correct spatiotemporal regulation of IL-7 signaling is important for T cell development.