Interleukin-7 receptor subunit alpha (IL-7Rα) (IL-7Rα)

The Interleukin-7 receptor subunit alpha (IL-7Rα), also known as CD127, is a type I cytokine receptor that forms a functional heterodimer with the common gamma chain (γc) to mediate IL-7 signaling (UniProt P16871). The cytoplasmic signaling domain of IL-7Rα is the intracellular portion responsible for initiating downstream cascades; it contains a Box 1 motif for Janus kinase 1 (JAK1) association and a critical tyrosine residue (Y449) that recruits STAT5 and PI3K upon phosphorylation (PubMed: 21909101). This domain is essential for the survival, development, and homeostatic proliferation of T cells and B cells. Somatic gain-of-function mutations in the cytoplasmic signaling domain, such as cysteine insertions that lead to ligand-independent dimerization, are a hallmark of T-cell acute lymphoblastic leukemia (T-ALL) (PubMed: 21909101). Furthermore, dysregulation of this domain's signaling is implicated in autoimmune diseases like multiple sclerosis (PubMed: 17660530). Therapeutic interventions, including monoclonal antibodies like lusvertikimab, target the receptor to prevent the activation of this cytoplasmic signaling domain, thereby inhibiting pathological cell proliferation and inflammation (OSE Immunotherapeutics).

Other names

CD127IL7RIL-7RACDW127Interleukin-7 receptor alpha chain

Antagonism of the IL-7 receptor to block IL-7-mediated signaling through the JAK/STAT and PI3K/Akt pathways.