Molecular regulation of common γ-chain / Interleukin-2 family cytokine receptors

Cytokines are small secreted proteins that mediate intercellular communication. Among numerous cytokines, members of the common γ-chain (γ c ) family have emerged as key regulators of immune responses. This family consists of Interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21, which each perform pleiotropic functions by regulating the differentiation, proliferation, and function of different immune cells, and are consequently involved in a variety of pathomechanisms. The complex functions of each cytokine depend on the expression of shared and individual receptors. Here, we describe how the receptors of the γ c family are regulated, focusing on posttranslational mechanisms. We summarize how their function is modulated by soluble receptors and glycosylation, and how their signaling ability is regulated by receptor internalization and degradation. Additionally, we describe how intrafamily crosstalk regulates the expression of the receptors. Finally, we discuss how knowledge of receptor regulation can be used to develop new therapeutic approaches. • The Interleukin-2/common γ-chain (γ c ) family consists of six cytokines that are essential regulators for healthy and pathologic immune responses • The activity of each cytokine is mediated via a specific receptor complex • The receptors of the γ c family are regulated by their soluble counterparts, glycosylation, internalization, and intrafamily crosstalk • Knowledge on the receptor regulation can be exploited for the development of novel therapeutics