Interleukin-4 receptor subunit alpha (IL-4Rα) within the Progesterone-Induced Blocking Factor (PIBF) receptor complex (IL-4Rα/PIBFR)

The Interleukin-4 receptor subunit alpha (IL-4Rα) is a critical signaling component that forms a functional complex with the Progesterone-Induced Blocking Factor (PIBF), a protein essential for maintaining maternal-fetal tolerance during pregnancy. PIBF is produced by lymphocytes in response to progesterone and binds to a receptor complex containing IL-4Rα to activate the JAK/STAT6 pathway, which promotes a Th2-biased immune environment and prevents fetal rejection (Szekeres-Bartho et al., 2001, International Immunopharmacology). Beyond its reproductive role, the PIBF/IL-4Rα axis is frequently overexpressed in various malignancies, where it contributes to tumor cell survival, proliferation, and immune evasion (Kozma et al., 2006, Journal of Reproductive Immunology). While IL-4Rα is a well-known target for treating allergic diseases through drugs like dupilumab, its specific interaction within the PIBF receptor complex represents a specialized pathway for immunomodulation. Targeting this complex offers potential therapeutic avenues for addressing recurrent pregnancy loss and certain types of cancer that exploit this signaling mechanism for growth. Understanding the distinct stoichiometry and signaling of the PIBF-bound IL-4Rα is vital for developing precise interventions that do not broadly disrupt other IL-4 or IL-13 mediated functions.

Other names

IL4RACD124PIBF-RProgesterone-induced blocking factor receptorIL-4 receptor alpha chainSoluble IL-4 receptor subunit alpha

Competitive inhibition of the IL-4Rα subunit to prevent the assembly of the PIBF/IL-4Rα signaling complex, thereby blocking downstream JAK1/STAT6 activation and Th2-mediated cytokine production.