IL-3 induces basophil expansion in vivo by directing granulocyte-monocyte progenitors to differentiate into basophil lineage-restricted progenitors in the bone marrow and by increasing the number of basophil/mast cell progenitors in the spleen.
Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL-3 plus anti-IL-3 Ab) greatly facilitated the differentiation of GMPs into basophil lineage-restricted progenitors (BaPs) but not into eosinophil lineage-restricted progenitors or mast cells in the bone marrow. We also found that the IL-3 complex treatment resulted in approximately 4-fold increase in the number of basophil/mast cell progenitors (BMCPs) in the spleen. IL-3-driven basophil expansion depended on STAT5 signaling. We showed that GMPs but not common myeloid progenitors expressed low levels of IL-3 receptor. IL-3 receptor expression was dramatically up-regulated in BaPs but not eosinophil lineage-restricted progenitors. Approximately 38% of BMCPs expressed the IL-3R alpha-chain. The up-regulated IL-3 receptor expression was not affected by IL-3 or STAT5. Our findings demonstrate that IL-3 induced specific expansion of basophils by directing GMPs to differentiate into BaPs in the bone marrow and by increasing the number of BMCPs in the spleen.
Ohmori
Keitaro
K
Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
Luo
Yuchun
Y
Jia
Yi
Y
Nishida
Jun
J
Wang
Zhengqi
Z
Bunting
Kevin D
KD
Wang
Demin
D
Huang
Hua
H
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007377:Interleukin-3 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D007377:Interleukin-3; D016185:Receptors, Interleukin-3