Common cytokine receptor gamma chain family (gamma-c family receptors)

The IL-7/IL-15 family cytokine receptors, more formally known as the common gamma chain (gamma-c) receptor family, are a group of type I cytokine receptors that share the common gamma chain (CD132) subunit. This family includes receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, with IL-7 and IL-15 being particularly critical for T-cell and natural killer (NK) cell development and homeostatic maintenance. The IL-7 receptor (IL-7R) is a heterodimer of IL-7Ra (CD127) and gamma-c, while the IL-15 receptor (IL-15R) is a heterotrimer consisting of IL-15Ra (CD215), IL-2/15Rb (CD122), and gamma-c. Signaling through these receptors primarily involves the activation of Janus kinases JAK1 and JAK3, leading to the phosphorylation and nuclear translocation of STAT5. Therapeutically, these receptors are major targets in oncology and immunology. Agonists, such as recombinant IL-7 (e.g., efineptakin alfa) and IL-15 superagonists (e.g., N-803), are being developed to boost immune responses against tumors and chronic infections by expanding T-cell and NK-cell populations. Conversely, antagonists and antibodies targeting specific subunits (like CD127 or CD122) or the downstream JAK/STAT pathway are used or investigated for treating autoimmune diseases, such as rheumatoid arthritis and celiac disease, as well as lymphoid malignancies like T-cell acute lymphoblastic leukemia (T-ALL).

Other names

IL-7/IL-15 family cytokine receptorsCommon gamma chain receptor familyCD132 family receptorsInterleukin-2 receptor subunit gamma familyType I cytokine receptor family (gamma-c subset)

Agonism of specific receptor complexes (e.g., IL-7R or IL-15R) to activate the JAK1/JAK3 and STAT5 signaling pathways, promoting the survival and expansion of T cells and natural killer (NK) cells; Antagonism of receptor subunits or inhibition of downstream Janus kinases to suppress pathological immune activation or malignant lymphoid cell growth.