Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics

[Display omitted] •Monocytes and macrophages are in part responsible for sex differences in asthma.•Greater expression of γC and CX3CR1 on monocytes from asthmatic women than men.•Higher IL-4-induced M2 gene expression in macrophages from asthmatic women than men.•Reduced SOCS1 in lung macrophages from asthmatics than from healthy controls. Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression ofγC, part of the type I IL-4 receptor, and reduced IL-4–induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.