Role of basophils in Th17 cell differentiation and function

Abstract

Basophils are rare circulating granulocytes and have been proposed to be involved in T helper (Th) 2 type immunity mainly through interleukin-4 (IL-4) secretion. In addition to IL-4, it has been known that basophils produce IL-6 and TNF- $\alpha$ with immunoglobulin E (IgE) crosslink. Th17 cell development is achieved with the action of IL-6 and transforming growth factor- $\beta$ (TGF- $\beta$). Whether the capacity of basophils to produce IL-6 is involved in the differentiation of Th17 cells is unknown. The aim of this study is to determine the role of basophils on Th cell differentiation especially Th17 cell development and plasticity of Th subsets by using in vitro T cell differentiation and cholera toxin (CT) mediated Th17 inflammation model. Bone marrow derived basophils (BMBs) as well as splenic basophils produced large amount of IL-4 and IL-6 by stimulation with IgE crosslink and CT. BM-Bs have additional role of Th17 cell differentiation helping DC through secretion of IL-6 in vitro culture system in the presence of TGF- $\beta$. Furthermore, BM-B mediated Th17 cell differentiation effects were prominent in cholera toxin induced-Th17 dominated lung infection model. Our results indicate that basophil is an important inducer of Th17 cell differentiation, which is dependent on IL-6 secretion.