Estriol reduces pulmonary immune cell recruitment and inflammation to protect female mice from severe influenza

Meghan S. Vermillion, Rebecca L. Ursin, Sarah E. Attreed, Sabra L Klein

Research output: Contribution to journalArticle

Abstract

Estriol (E3) is an endogenous estrogen in females with broad biological activity within diverse tissue types. In the context of certain T-cell–mediated autoimmune inflammatory diseases, E3 can ameliorate disease severity through immunomodulatory mechanisms that decrease tissue inflammation. Severe disease caused by influenza A virus (IAV) infection is also characterized by aberrant inflammation and immunopathology. How E3 might affect the pathogenesis of IAV infection, however, has not been explored. Gonadally intact female C57BL/6 mice that were treated with exogenous E3 during infection with mouse-adapted 2009 H1N1 had reduced total pulmonary inflammation and improved disease outcomes compared with females that received no hormone. Furthermore, compared with no hormone treatment, E3 treatment reduced the induction of genes associated with proinflammatory cytokine and chemokine responses in the lungs, which preceded clinical disease, reductions in innate immune cell recruitment, altered pulmonary T-cell skewing, and reduced antibody titers during IAV infection. Although E3 treatment was associated with reduced local and systemic anti-influenza adaptive immune responses, there was no effect of E3 on viral replication or clearance. Together, these data suggest that exogenous E3 confers protection during IAV infection through immunomodulatory mechanisms and that E3 may have broad therapeutic potential in the context of both infectious and noninfectious inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)3306-3320
Number of pages15
JournalEndocrinology
Volume159
Issue number9
DOIs
StatePublished - Jan 1 2018

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Estriol
Human Influenza
Influenza A virus
Virus Diseases
Inflammation
Lung
Hormones
Adaptive Immunity
Inbred C57BL Mouse
Chemokines
Autoimmune Diseases
Pneumonia
Estrogens
Cytokines
T-Lymphocytes
Antibodies
Infection
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Estriol reduces pulmonary immune cell recruitment and inflammation to protect female mice from severe influenza. / Vermillion, Meghan S.; Ursin, Rebecca L.; Attreed, Sarah E.; Klein, Sabra L.

In: Endocrinology, Vol. 159, No. 9, 01.01.2018, p. 3306-3320.

Research output: Contribution to journalArticle

Vermillion, Meghan S. ; Ursin, Rebecca L. ; Attreed, Sarah E. ; Klein, Sabra L. / Estriol reduces pulmonary immune cell recruitment and inflammation to protect female mice from severe influenza. In: Endocrinology. 2018 ; Vol. 159, No. 9. pp. 3306-3320.
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