IL-13Rα1 is a surface marker for M2 macrophages influencing their differentiation and function

In this study, we examined the role IL-13 receptor alpha 1 (IL-13R1) plays in macrophage differentiation and function. The findings indicate that IL-13R1 is expressed on the M2 but not on the M1 subset of macrophages and specifically heterodimerizes with the IL-4R chain to form a type II receptor, which controls the differentiation and function of these cells. Indeed, BM cells from IL-13R1(+/+) and IL-13R1(-/-) mice yield equivalent numbers of macrophages when cultured under M2 polarizing conditions. However, IL-13R1(-/-) BM cells yield a much higher number of macrophages than IL-13R1(+/+) BM cells when the differentiation is carried out under M1-polarizing conditions. Further analyses indicated that macrophages that express IL-13R1 also display surface markers associated with an M2 phenotype. In addition, the IL-13R1(+) macrophages were highly efficient in phagocytizing zymosan bioparticles both in vitro and in vivo, and supported differentiation of naive T cells to a Th2 phenotype. Finally, when stimulated by IL-13, a cytokine that uses the heteroreceptor, the cells were able to phosphorylate STAT6 efficiently. These previously unrecognized findings indicate that IL-13R1 serves as a marker for M2 macrophages and the resulting heteroreceptor influences both their differentiation and function.