Interleukin-7 (IL-7) is a secreted gamma-chain cytokine encoded in humans by the IL7 gene on chromosome 8q12-13. It is produced constitutively by stromal cells in bone marrow, thymus, spleen and intestinal mucosa, as well as by vascular endothelial cells, and is presented in the extracellular matrix as a soluble ligand. IL-7 signals through a hematopoietic cell-surface receptor composed of the IL-7-specific alpha chain IL-7Ralpha (CD127) non-covalently associated with the common gamma chain (gamma c, CD132), which is shared with the receptors for IL-2, IL-4, IL-9, IL-15 and IL-21. IL-7Ralpha is constitutively associated with JAK1 and gamma c with JAK3; ligand binding activates these kinases, which phosphorylate receptor tyrosines and recruit and activate STAT5A/STAT5B, with ancillary activation of PI3K-Akt and MAPK cascades. STAT5 dimers up-regulate anti-apoptotic BCL-2 family members and drive lineage gene programs. In humans, IL-7 is non-redundant for T-cell development in the thymus (survival of early thymocyte progenitors and of TCR-alpha beta selection) and for homeostasis and survival of naive and memory peripheral T cells, but it is not required for human B-cell development (in contrast to the mouse, where it also drives B-lymphopoiesis). Loss-of-function mutations in IL7R or JAK3 cause severe combined immunodeficiency.