Epicutaneous Administration of 17β-Estradiol Induces Langerhans Cells Depletion

ABSTRACT

Background

Langerhans cells (LC) number and function in mouse vaginal mucosa are affected by 17β-estradiol (E₂) application; nonetheless, its effect on epidermal LC has not been studied. The purpose of this study was to evaluate the effect of topical administration of E₂ on the number, phenotype, and migratory ability of LC in mouse skin.

Methods

Ears of adult CD1 male mice were topically treated once with several doses. Immunohistochemical staining for CD207 and TUNEL staining were performed. LC migration to lymph nodes and the effect on the expression of costimulatory molecules on cultured dendritic cells (DC) were also evaluated.

Results

E₂ decreased the number of CD207+ LC in a dose-dependent manner. One hour after treatment, 1 and 10 µg/mL E₂ significantly reduced the LC number by 21% and 26%, respectively, after two hours, the reduction was 23% and 41%, respectively. After 48 hours, LC recovered, and after 96 hours of treatment, the CD207+/MHCII+ DC numbers were increased in regional lymph nodes. However, CD86 and CD40 molecules were expressed at lower levels than in positive control. The TUNEL assay did not show apoptotic cells. Furthermore, in cultured DC, E₂ promoted a decrease in CD40 and CD86 expression and an increase in CD273, CD274, MHCII, and CCR7.

Conclusions

The topical administration of E₂ induced a transitory local diminution of LC population and a tolerogenic phenotype. This decrease in epidermal LC suggests that E₂ may affect skin immune responses, inducing an inhibitory response, which should be considered when prescribing topical E₂ medications.

KEYWORDS:

• 17β-estradiol
• dendritic cells
• estrogens
• Langerhans cells
• skin immune system

Acknowledgments

The authors are thankful to Sara Judith Alvarez-Pérez and Lorena Mendiola-Almaráz for their technical assistance.

Authorship

KJY and MHE contributed equally to the development of the experiments and the writing and revision of the article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by DGAPA/PAPIIT-UNAM under Grants [IN221419] and [IN218315].