Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation

Mireya Becerra-Diaz, Ashley B. Strickland, Aleksander Keselman, Nicola Mary Heller

Research output: Contribution to journalArticle

Abstract

Allergic asthma is a disease initiated by a breach of the lung mucosal barrier and an inappropriate Th2 inflammatory immune response that results in M2 polarization of alveolar macrophages (AM). The number of M2 macrophages in the airway correlates with asthma severity in humans. Sex differences in asthma suggest that sex hormones modify lung inflammation and macrophage polarization. Asthmatic women have more M2 macrophages than asthmatic men and androgens have been used as an experimental asthma treatment. In this study, we demonstrate that although androgen (dihydrotestosterone) reconstitution of castrated mice reduced lung inflammation in a mouse model of allergic lung inflammation, it enhanced M2 polarization of AM. This indicates a cell-specific role for androgens. Dihydrotestosterone also enhanced IL-4-stimulated M2 macrophage polarization in vitro. Using mice lacking androgen receptor (AR) in monocytes/macrophages (ARfloxLysMCre), we found that male but not female mice exhibited less eosinophil recruitment and lung inflammation due to impaired M2 polarization. There was a reduction in eosinophil-recruiting chemokines and IL-5 in AR-deficient AM. These data reveal an unexpected and novel role for androgen/ AR in promoting M2 macrophage polarization. Our findings are also important for understanding pathology in diseases promoted by M2 macrophages and androgens, such as asthma, eosinophilic esophagitis, and prostate cancer, and for designing new approaches to treatment.

Original languageEnglish (US)
Pages (from-to)2923-2933
Number of pages11
JournalJournal of Immunology
Volume201
Issue number10
DOIs
StatePublished - Nov 15 2018

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Androgen Receptors
Androgens
Pneumonia
Macrophages
Asthma
Alveolar Macrophages
Dihydrotestosterone
Eosinophils
Eosinophilic Esophagitis
Interleukin-5
Gonadal Steroid Hormones
Chemokines
Sex Characteristics
Interleukin-4
Monocytes
Prostatic Neoplasms
Pathology
Lung
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation. / Becerra-Diaz, Mireya; Strickland, Ashley B.; Keselman, Aleksander; Heller, Nicola Mary.

In: Journal of Immunology, Vol. 201, No. 10, 15.11.2018, p. 2923-2933.

Research output: Contribution to journalArticle

Becerra-Diaz, Mireya ; Strickland, Ashley B. ; Keselman, Aleksander ; Heller, Nicola Mary. / Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation. In: Journal of Immunology. 2018 ; Vol. 201, No. 10. pp. 2923-2933.
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