Iron metabolism In Dendritic Cells is important for Induction of Follicular Helper T Cell Subsets in Allergy

Introduction/Rationale: Allergic asthma affects 25 million of people in the United States and 300 million people worldwide. There are treatments to reduce symptomology, but currently there is no cure. Thus, additional research is warranted. Dendritic cells (DCs) are crucial bridges between the innate and adaptive immune systems, capturing antigens, processing them, and presenting them to T cells. They are crucial to initiating and shaping adaptive immune responses. Follicular T helper cells (Tfh) are a specialized subset of CD4+ helper T cells that are important in the development of antibody-producing B cells. CD71, the transferrin receptor, is a cell surface glycoprotein that plays a crucial role in iron uptake. Tfh13 cells are the specialized subset of Tfh that induce production of high affinity IgE. Here, we hypothesized that iron uptake was important for Tfh polarization, especially Tfh13 polarization.

Methods: C57/BL6 mice were treated with Ferristatin II intranasally to inhibit iron uptake prior to the allergen extract, Alternaria alternata administered intranasal. The mice were also treated with Deferiprone, a cell permeable iron chelator, intraperitonially prior to the intranasal instillation of allergen extract, Alternaria alternata. On day 8, lymphadenectomy was performed, cells were processed for Flow cytometry, and data analysis was done using Flowjo. Statistical analyses were performed using Ordinary One-way ANOVA.

Results: With Ferristatin II treatment, we saw significant decrease in differentiation to Tfh13, while Tfh2 and Th2 cells were not significantly affected. with Deferiprone, a cell permeable iron chelator, we observed significant differences in Tfh2 and Tfh13 while Th2 cells were unchanged. We also observed a novel subset of allergen-carrying CD71hi cDC2 in the draining lymph node after allergen sensitization by flow cytometry.

Conclusion: CD71hi cDC2 population may be important for the polarization of the T follicular helper cells, thereby influencing antibody production of B cells.