The common cytokine receptor gamma-chain family consists of six members, IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. All members of this family signal through receptor complexes that contain the common cytokine receptor gamma-chain subunit. The receptors for IL-4, IL-7, IL-9, and IL-21 are heterodimeric complexes consisting of the common gamma-chain and a unique cytokine-specific subunit. The receptors for IL-2 and IL-15 are heterotrimeric complexes consisting of either IL-2 R alpha or IL-15 R alpha, IL-2/IL-15 R beta and the common gamma-chain. Signaling pathways activated by this cytokine family include the PI 3-K-Akt pathway, the Ras-MAPK pathway, and the Jak-STAT pathway.
Common gamma-chain family cytokines are essential for the establishment and maintenance of normal immune system functions. They have both unique and overlapping effects on a number of cell types including T cells, B cells, natural killer cells, mast cells, and myeloid and erythroid progenitors. IL-2 was initially identified as a T cell growth factor, and has since been shown to play a critical role in maintaining T cell homeostasis and preventing self-reactivity. IL-4 is required for Th2 and Th9 cell differentiation, regulates immunoglobulin class switching, and promotes mast cell survival and proliferation. IL-7 is required for T cell development and homeostatic proliferation, mouse B cell development, and the generation of memory T cells. IL-9 promotes mouse T cell and mast cell growth, regulates B cell immunoglobulin production, enhances mast cell protease expression, and promotes goblet cell hyperplasia and mucus production. IL-15 is required for the development, survival, and activation of natural killer cells, the homeostasis of natural killer T cells and intraepithelial lymphocytes, and the maintenance of naïve and memory CD8+ T cells. The most recently described member of this family, IL-21 has been shown to be required for Th17 cell differentiation and the generation of T follicular helper cells. In addition, it regulates B cell activities and the cytotoxicity of CD8+ T cells and natural killer cells.