Interleukin-5 receptor subunit alpha (IL5RA) (IL5RA)

Eosinophil survival signaling is a critical biological process primarily mediated by the Interleukin-5 (IL-5) receptor complex, which is essential for the maturation, activation, and persistence of eosinophils in the blood and tissues (UniProt Q01344). The signaling is initiated when the cytokine IL-5 binds to the Interleukin-5 receptor subunit alpha (IL5RA), leading to the recruitment of the common beta subunit (CSF2RB) and the activation of downstream intracellular pathways, including JAK2-STAT5, PI3K-Akt, and Raf-1/MEK/ERK (PubMed: 16461133). These pathways collectively inhibit apoptosis by upregulating anti-apoptotic proteins such as Mcl-1 and Bcl-xL, thereby extending the lifespan of eosinophils from a few days to several weeks in inflammatory environments (PubMed: 25631330). Dysregulation of this signaling axis is a hallmark of eosinophilic diseases, including severe eosinophilic asthma, hypereosinophilic syndrome (HES), and eosinophilic granulomatosis with polyangiitis (EGPA). Therapeutic intervention typically involves monoclonal antibodies that either neutralize the IL-5 ligand (e.g., mepolizumab, reslizumab) or target the IL5RA receptor directly (e.g., benralizumab), the latter of which also induces eosinophil depletion via antibody-dependent cell-mediated cytotoxicity (ADCC) (DrugBank DB06608).

Other names

IL-5 receptor alphaCD125IL5REosinophil survival signaling pathway

Antagonism of the IL-5 receptor or neutralization of the IL-5 ligand to inhibit downstream signaling pathways (JAK/STAT, PI3K/Akt) that prevent eosinophil apoptosis.