IL-3 Expands Pre-Basophil and Mast Cell Progenitors by Upregulating the IL-3 Receptor Expression

Basophils and mast cells play a critical role in allergic inflammation and provide protective immunity against certain types of parasitic infections. Expansion of basophils and mast cells to the critical numbers is believed to be an essential step in enabling basophils and mast cells to carry out their protective functions. However, factors that drive basophil and mast cell expansion are still incompletely understood. We tested the roles of cytokines and growth factors IL-3, TSLP, GM-CSF, IL-5, SCF, IL-7, IL-25, and IL-33 in promoting the differentiation of pre-basophil and mast cell progenitors (pre-BMPs)in vitro.We found that while GM-CSF only expanded basophils, IL-3 promoted the differentiation of pre-BMPs into both basophils and mast cells. We found that IL-3 expanded the number of pre-BMPsin vivo. We showed that IL-3 upregulatedIl3ramRNA and protein expression on pre-BMPs, supporting that IL-3 expands pre-BMPs in part by upregulating the IL-3 receptor expression. Although Gata2 mRNA expression was upregulated by IL-3 treatment in pre-BMPs, it is dispensable for IL-3-mediated upregulation of IL-3 receptor expression. Our study reveals a novel mechanism through which IL-3 expands basophil and mast cells.