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

Mireya Becerra-Díaz, Andrew D. Lerner, Diana H. Yu, Jeffrey P. Thiboutot, Mark C. Liu, Lonny B. Yarmus, Sonali Bose, Nicola M. Heller

Research output: Contribution to journalArticlepeer-review

Abstract

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 of γC, 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.

Original languageEnglish (US)
Article number104252
JournalCellular Immunology
Volume360
DOIs
StatePublished - Feb 2021

Keywords

  • Allergic lung inflammation
  • Alveolar macrophages
  • Asthma
  • Cell recruitment
  • Chemokine
  • Hormones
  • IL-4
  • Monocytes
  • Sex differences

ASJC Scopus subject areas

  • Immunology

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