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* Division of Allergy and Immunology, Departments of Medicine, National Jewish Health, Denver, CO 80206;
Departments of Medicine, Case Western Reserve University, Cleveland, OH 44106;
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226;
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226; and
¶ Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80206
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 
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
-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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported by grants from the National Institutes of Health R01 AI48568 and R01 AI068083 (H.H.), R01 HL073284 and R01 AI079087 (D.W.), Scholar Award from the Leukemia & Lymphoma Society (D.W.), and R01DK059380 (K.B.).
2 Current address: Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, Japan.
3 Address correspondence and reprint requests to Dr. Hua Huang, Departments of Medicine and Immunology, National Jewish Health and University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: huangh{at}njc.org
4 Abbreviations used in this paper: BaP, basophil lineage-restricted progenitor; BMCP, basophil/mast cell progenitor; CMP, common myeloid progenitor; EoP, eosinophil lineage-restricted progenitor.
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  S. Kim, T. Shen, and B. Min Basophils Can Directly Present or Cross-Present Antigen to CD8 Lymphocytes and Alter CD8 T Cell Differentiation into IL-10-Producing Phenotypes J. Immunol., September 1, 2009; 183(5): 3033 - 3039. [Abstract] [Full Text] [PDF]
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