Common Gamma-Chain Receptor Family Review

The common cytokine receptor gamma chain (γc) family, which consists of interleukin 2 (IL-2), IL-4, IL-7, IL-9, IL-15 and IL-21, and is so named because the receptors for these cytokines share gamma-chain (also known as IL-2Rγ and CD132).

The common gamma-chain (γc) is critical for ligand binding and signaling by common gamma-chain (γc) cytokines. All γc family cytokines similarly activates the Janus kinase (JAK)-family protein tyrosine kinases JAK1 and JAK3, with JAK1 binding a unique α or β chain and JAK3 binding the common gamma-chain (γc). They exert its effect through interaction with gamma-chain (γc) cytokine receptor complex, which is composed of a unique receptor chain and the common gamma-chain (γc).

Below will briefly discuss each common gamma-chain (γc) receptor family member and their functions, including common gamma-chain receptor, IL-4R, IL-7R, IL-9R, IL-15R and IL-21R.

common gamma-chain receptor family

Common Gamma-Chain Receptor

The common gamma-chain (γc) was first discovered as a component of the receptor for IL-2, the prototypic member of this family. The IL-2 receptor (IL-2R) consists of three chains, which together form the high-affinity IL-2R complex, but which in other combinations bind IL-2 with low affinity (IL-2Rα alone) or intermediate affinity (IL-2Rβ and γc).

The common gamma-chain receptor is the only cytokine receptor that is encoded in the X chromosome. Because gamma-chain receptor is subject to X chromosome inactivation, gamma-chain receptor shows monoallelic expression and provides the genetic explanation for X-linked severe combined immunodeficiency (X-SCID).

However, the immune defects in patients with X-SCID are much more severe than those of humans or mice lacking IL-2, in which the development of T and NK cells is intact, originally led to the hypothesis and subsequent confirmation that γc was shared by multiple cytokines.

Other Receptors In Common Gamma-Chain Receptor Family

IL-4R

Combined with the common gamma-chain (γc), IL-4 receptor (IL-4R) becomes an IL-4 receptor complex. The effects of interleukin 4 (IL-4) depend upon binding to and signaling through this receptor complex, resulting in a series of phosphorylation events mediated by receptor-associated kinases. IL-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses.

IL-7R

The IL-7 receptor complex consists of two subunits, IL-7 receptor (IL-7R) and common gamma-chain (γc). IL-7R signaling through is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Some publications demonstrated that soluble IL-7R is closely related with rheumatoid arthritis and multiple sclerosis autoimmune disease.

IL-9R

The IL-9 receptor complex is composed of ligand specific IL-9 receptor (IL-9R) and common gamma-chain (γc). The functions of IL-9 are mediated by the IL-9 receptor complex. IL-9 plays a role in asthma and allergy.

IL-15R

The IL-15 receptor complex consists of IL-15 receptor (IL-15R), IL-2R beta chain and common gamma-chain (γc). Signaling through the IL-15/IL-15R system is of profound clinical importance has become amply clear in rheumatoid arthritis (RA), where IL-15 antibodies have already been tested in Phase I/II trials.

IL-21R

Like other common gamma-chain receptor family members, the IL-21 receptor complex also contains IL-21 receptor (IL-21R) and common gamma-chain (γc). IL-21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding.

References

1. Waickman, A. T., Park, J. Y., & Park, J. H. (2016). The common γ-chain cytokine receptor: tricks-and-treats for T cells. Cellular and molecular life sciences, 73(2), 253-269.
2. Lee, B., & Hong, C. (2015). The role of soluble common gamma chain in autoimmune disease. Anatomy & cell biology, 48(1), 10-15.
3. Rochman, Y., Spolski, R., & Leonard, W. J. (2009). New insights into the regulation of T cells by γc family cytokines. Nature reviews. Immunology, 9(7), 480.
4. Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. (1999). The IL-4 receptor: signaling mechanisms and biologic functions. Annual review of immunology, 17(1), 701-738.
5. Budagian, V., Bulanova, E., Paus, R., & Bulfone-Paus, S. (2006). IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine & growth factor reviews, 17(4), 259-280.