J Clin Cell Immunol. 2015;6(6):1-9. doi: 10.4172/2155-9899.1000372.
ER.
Journal of clinical & cellular immunology
Sally Huber
Affiliations
Affiliations
- Department of Pathology, University of Vermont, Colchester, Vermont 05446, USA.
PMID: 26925301
PMCID: PMC4765002 DOI: 10.4172/2155-9899.1000372
Abstract
OBJECTIVES: Coxsackievirus B3 (CVB3) induced myocarditis is sex dependent with males developing more severe disease than females. Previous studies had shown that sex-associated hormones determine the sex bias with testosterone and progesterone promoting myocarditis while estrogen (E2) is protective. There are two major estrogen receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). The goal of the current study was to determine the relative role of these receptors to myocarditis susceptibility and the mechanism of their action.
METHODS: Female C57Bl/6 wild-type mice and C57Bl/6 mice deficient in ERα, or ERβ were infected intraperitoneally with 102 plaque forming units CVB3. After 7 days, hearts were evaluated for virus titers by plaque forming assay and myocardial inflammation. Lymphoid cells either from the spleen or infiltrating the heart were characterized by labeling with antibodies including CD4, CD25, FoxP3, IFNγ, IL-4, CD11b, CD1d, Vγ4, TCRβ, or with CD1d-tetramer and evaluated by flow cytometry. To confirm that signaling through distinct estrogen receptors controlled myocarditis susceptibility and T-regulatory cell response, male C57Bl/6 mice were treated with the ERα-specific agonist, propyl pyrazole triol (PPT), ERβ agonist, diarylpropionitrile (DPN), or 17-β-estradiol (E2) as a non-specific estrogen receptor agonist.
RESULTS: Myocarditis, cardiac virus titers, and CD4
CONCLUSION: These results demonstrate that ERα and ERβ both modulated CVB3 myocarditis susceptibility but in opposite directions and that their predominant effect is mediated through their ability to alter NKT and Vγ4
Keywords: CD4+ cells; Coxsackievirus B3; Estrogen receptor alpha; Estrogen receptor beta; Immunosuppression; Myocarditis; T-regulatory cells
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