β-Glucosylceramides and Tocopherols Regulate Development and Function of Dendritic Cells

Area of Science:

• Immunology
• Developmental Biology
• Nutritional Science

Background:

• Offspring of allergic mothers have increased allergy predisposition.
• Elevated maternal β-glucosylceramides (βGlcCers) are linked to fetal and offspring immune alterations.
• Tocopherols (α- and γ-tocopherol) can modify these allergy-associated effects.

Purpose of the Study:

• To investigate if βGlcCers and tocopherols directly regulate dendritic cell (DC) development.
• To elucidate the mechanisms underlying βGlcCer and tocopherol effects on DCs.

Main Methods:

• In vitro culture of mouse bone marrow-derived DCs (BMDCs) with βGlcCers and tocopherols.
• Analysis of DC development, costimulatory molecule expression, and protein kinase C (PKC) activation.
• Ex vivo assessment of antigen processing and T cell proliferation in DCs from offspring of allergic mothers.

Main Results:

• βGlcCers increased BMDC numbers and PKCα/PKCδ activation.
• α-tocopherol blocked βGlcCer-induced BMDC expansion and PKC activation.
• γ-tocopherol potentiated βGlcCer effects on BMDC numbers and PKCδ activation.
• Offspring of allergic mothers showed increased CD11b+CD11c+ DCs and enhanced T cell proliferation.

Conclusions:

• βGlcCer directly promotes DC development and PKC activation, contributing to allergic predisposition in offspring.
• Dietary tocopherols modulate these βGlcCer-mediated effects on DCs.
• Findings suggest potential for tocopherol-based interventions in allergic diseases.