615 - Maternal lipids regulate neonatal dendritic cells during development of allergic disease

Poster Number: 615
Publication Number: 615.200

Jacquelyn D. Lajiness, Indiana University, Indianapolis, IN, United States; Isaac Tat, Indiana University School of Medicine, Indianapolis, IN, United States; Joan Cook-Mills, Indiana University School of Medicine, Indianapolis, IN, United States

Background: In humans and mice, offspring of allergic mothers are predisposed to development of allergy. In mice, allergic mothers have elevated β-glucosylceramides (βGlcCer) that are transported to the fetus. Elevated βGlcCer in offspring is associated with increased CD11c+CD11b+ dendritic cells (DCs) and increased allergic lung inflammation after antigen exposure. We have previously shown that maternal dietary supplementation with α-tocopherol (αT) decreases while γ-tocopherol (γT) increases offspring allergic inflammation. However, it is not known whether βGlcCer and tocopherols directly regulate development of DCs or which signaling pathways may be involved.

Objective: We hypothesize that βGlcCer increases development of DC subsets via protein kinase C (PKC) activation.

Design/Methods: We treated mouse bone marrow cultures with βGlcCer and tocopherol isoforms during generation of DCs. DC phenotypes and intracellular signaling were analyzed by immunolabeling and flow cytometry using CD45, CD11b, Ly6c, CD11c, and MHCII markers.

Results: We demonstrate in vitro treatment with βGlcCer increases CD11c+CD11b+ DC subsets including monocyte-derived DCs (mDCs) by 12±0.7 fold and resident phenotype DCs (rDCs) by 8±1.3 fold. Similarly, treatment with γT increases mDC and rDC by 7±1.3 fold and 3.4±0.5 fold respectively, but there was no difference observed in groups treated with αT. Interestingly, administration of αT mitigated the βGlcCer-induced increase in mDCs and rDCs, while γT potentiated the increase in the number of mDCs and rDCs observed with βGlcCer treatment. Furthermore, βGlcCer increased PKCα and PKCδ activation in mDCs and rDCs that was blocked by αT. In contrast, γT increased PKCα and PKCδ activation in mDCs and rDCs. Conclusion(s): Our work identifies maternal lipids as important factors that directly modulate DC differentiation which is critical in establishing the allergic phenotype in offspring of allergic mothers. These data shed light on mechanistic effects of environmental factors including maternal lipids on DC populations and how this may serve to promote allergic disease in offspring. They also suggest that tocopherols are a target for potential intervention in the maternal or postnatal diet that can be further tested as a protective measure to decrease development of allergic disease in offspring of allergic mothers.