• Human interleukin 5 (IL5) is a secreted cytokine that functions as a disulfide-linked homodimer and has long been referred to as an eosinophil differentiation factor. IL5 is produced predominantly by activated Th2 cells, and can also be secreted by group 2 innate lymphoid cells (ILC2), mast cells, and eosinophils under certain inflammatory contexts. IL5 is a key regulator of eosinophil biology, exerting prominent effects on eosinophil lineage commitment, expansion, maturation, trafficking, and survival.
• IL5 signals through the IL5 receptor, a heterodimer composed of a ligand-specific alpha chain (IL5Rα/IL5RA), which confers binding specificity, and a shared common beta chain (βc/CD131/CSF2RB), which is also used by the IL3 and GM-CSF receptors and mediates signal transduction. Upon receptor engagement, IL5 activates canonical pathways including JAK2–STAT5, PI3K/AKT, and RAS–MAPK, thereby promoting proliferation, differentiation programs, and anti-apoptotic survival signals.
• In the bone marrow, IL5 acts most strongly at relatively late stages of eosinophilopoiesis, preferentially expanding committed eosinophil progenitors and driving terminal differentiation, leading to increased output of mature eosinophils. In peripheral blood and tissues, IL5 further supports eosinophil persistence by inhibiting apoptosis and can “prime” eosinophils for enhanced effector functions, such as heightened responsiveness to inflammatory stimuli and increased degranulation capacity, thereby amplifying eosinophil-associated immune responses.
• The full coding sequences of human IL5 gene that was driven by CMV promoter were inserted into mouse TIGRE locus (Igs7) in B-NDG hIL5 mice.
• Human IL5 was only detectable in B-NDG hIL5 mice.
• Application: B-NDG hIL5 mice provides sustained human IL5 signaling in a humanized setting to promote development and functional maturation of human eosinophils from engrafted human CD34+ HSCs, enabling studies of eosinophil-driven disease mechanisms and in vivo evaluation of anti-IL5/IL5R therapeutics.

Gene targeting strategy for B-NDG hIL5 mice. The full coding sequences of human IL5 gene that was driven by CMV promoter were inserted into mouse TIGRE locus (Igs7) in B-NDG hIL5 mice.

Strain-specific IL5 expression analysis in wild-type B-NDG mice and homozygous B-NDG hIL5 mice by ELISA. Serum was collected from wild-type B-NDG mice (male, 11 weeks old, n=3) and homozygous B-NDG hIL5 mice (male, 8 weeks old, n=3). Expression level of human IL5 was analyzed by ELISA (anti-human IL5 antibody: R&D, D5000B). Human IL5 was only detectable in B-NDG hIL5 mice, but not in wild-type B-NDG mice.