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IL-4 Induces Differentiation and Expansion of Th2 Cytokine-Producing Eosinophils ¹

Luqiu Chen^2,*, Kristy A. Grabowski^2,*, Jun-ping Xin^*, John Coleman^*, Zan Huang^*, Baltazar Espiritu, Serhan Alkan, H. Bill Xie, Yuechun Zhu^*, Fletcher A. White^*, John Clancy, Jr^* and Hua Huang^3,*

Departments of ^* Cell Biology, Neurobiology and Anatomy, Medicine, and Pathology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153; and Department of Pathology, Duke University Medical Center, Durham, NC 27710

Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4⁺ T cells into CD4⁺ Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP⁺ cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP⁺ cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4⁺ T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.

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