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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #366996

Research Project: Reducing Peanut and Tree Nut Allergy

Location: Food Processing and Sensory Quality Research

Title: Peanut-specific IgE produced in a mouse food allergy model requires help from T follicular regulatory cells and IL-10 signaling by B cells

Author
item XIE, MARKUS - Indiana University Medical School
item LIU, HONG - Indiana University Medical School
item YANG, KAI - Indiana University Medical School
item KOH, BYUMGHEE - Indiana University Medical School
item WU, HAO - Indiana University Medical School
item Maleki, Soheila
item Hurlburt, Barry
item KAPLAN, MARK - Indiana University Medical School
item DENT, ALEXANDER - Indiana University Medical School

Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2020
Publication Date: 6/8/2020
Citation: Xie, M.M., Liu, H., Yang, K., Koh, B., Wu, H., Maleki, S.J., Hurlburt, B.K., Kaplan, M.H., Dent, A.L. 2020. Peanut-specific IgE produced in a mouse food allergy model requires help from T follicular regulatory cells and IL-10 signaling by B cells. Journal of Clinical Investigation. 130(7):3820-3832. https://doi.org/10.1172/JCI132249.
DOI: https://doi.org/10.1172/JCI132249

Interpretive Summary: Food allergies are a major clinical problem and are driven by the production of immunoglobulin E (IgE) antibodies specific for food antigens. High affinity antigen-specific antibodies develop from B cells within the germinal center (GC) reaction. T follicular regulatory (TFR) cells are a specialized subset of Foxp3+ T cells that modulate antibody responses in the GC. The function of TFR cells in the generation of food antigen-specific IgE are not well understood. Here we analyzed the role of TFR cells in regulating food antigen-specific IgE using a peanut antigen-based food allergy model in mice. Peanut-specific IgE levels and anaphylaxis responses were significantly blunted in TFR cell-deficient mice. Loss of TFR cells led to a marked increase in non-specific IgE levels, showing that TFR cells have both helper and suppressor functions on IgE production in the GC that work together to facilitate the production of antigen-specific IgE. Mice with augmented TFR cell responses had markedly higher levels of peanut-specific IgE, revealing an active helper function on antigen-specific IgE by TFR cells. The helper function of TFR cells involves the production of IL-10. Loss of IL-10 signaling by B cells led to a severely curtailed peanut-specific IgE response, decreased GC B cell survival and loss of B cells after peanut challenge. We thus reveal that TFR cells have an unexpected helper role in promoting food allergy and are a novel target for drug development.

Technical Abstract: Food allergies are a major clinical problem and are driven by the production of IgE antibodies specific for food antigens. High affinity antigen-specific antibodies develop from B cells within the germinal center (GC) reaction. T follicular regulatory (TFR) cells are a specialized subset of Foxp3+ T cells that modulate antibody responses in the GC. The function of TFR cells in the generation of food antigen-specific IgE are not well understood. Here we analyzed the role of TFR cells in regulating food antigen-specific IgE using a peanut antigen-based food allergy model in mice. Peanut-specific IgE titers and anaphylaxis responses were significantly blunted in TFR cell-deficient Foxp3-cre Bcl6-flox mice. Loss of TFR cells led to a marked increase in non-specific IgE levels, showing that TFR cells have both helper and suppressor functions on IgE production in the GC that work together to facilitate the production of antigen-specific IgE. Foxp3-cre Pten-flox mice with augmented TFR cell responses had markedly higher levels of peanut-specific IgE, revealing an active helper function on antigen-specific IgE by TFR cells. The helper function of TFR cells involves the production of IL-10. Loss of IL-10 signaling by B cells led to a severely curtailed peanut-specific IgE response, decreased GC B cell survival and loss of GC dark zone B cells after peanut challenge. We thus reveal that TFR cells have an unexpected helper role in promoting food allergy and are a novel target for drug development.