Josephine Scholz1,2, Julia Kuhrau2,3, Frederik Heinrich2, Gitta Anne Heinz2, Andreas Hutloff2,3,4, Margitta Worm1, Guido Heine1,2,5. 1. Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergy, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. 2. Deutsches Rheuma-Forschungszentrum, A Leibniz Institute, Berlin, Germany. 3. Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 4. Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. 5. Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Abstract
BACKGROUND: Vitamin A regulates the adaptive immune response and a modulatory impact on type I allergy is discussed. The cellular mechanisms are largely unknown. OBJECTIVE: To determine the vitamin A-responding specific lymphocyte reaction in vivo. METHODS: Antigen-specific B and T lymphocytes were analyzed in an adoptive transfer airway inflammation mouse model in response to 9-cis retinoic acid (9cRA) and after lymphocyte-specific genetic targeting of the receptor RARα. Flow cytometry, quantitative PCR, next-generation sequencing, and specific Ig-ELISA were used to characterize the cells functionally. RESULTS: Systemic 9cRA profoundly enhanced the specific IgA-secreting B-cell frequencies in the lung tissue and serum IgA while reducing serum IgE concentrations. RARα overexpression in antigen-specific B cells promoted differentiation into plasmablasts at the expense of germinal center B cells. In antigen-specific T cells, RARα strongly promoted the differentiation of T follicular helper cells followed by an enhanced germinal center response. CONCLUSIONS: 9cRA signaling via RARα impacts the allergen-specific immunoglobulin response directly by the differentiation of B cells and indirectly by promoting T follicular helper cells.
BACKGROUND:Vitamin A regulates the adaptive immune response and a modulatory impact on type I allergy is discussed. The cellular mechanisms are largely unknown. OBJECTIVE: To determine the vitamin A-responding specific lymphocyte reaction in vivo. METHODS: Antigen-specific B and T lymphocytes were analyzed in an adoptive transfer airway inflammationmouse model in response to 9-cis retinoic acid (9cRA) and after lymphocyte-specific genetic targeting of the receptor RARα. Flow cytometry, quantitative PCR, next-generation sequencing, and specific Ig-ELISA were used to characterize the cells functionally. RESULTS: Systemic 9cRA profoundly enhanced the specific IgA-secreting B-cell frequencies in the lung tissue and serum IgA while reducing serum IgE concentrations. RARα overexpression in antigen-specific B cells promoted differentiation into plasmablasts at the expense of germinal center B cells. In antigen-specific T cells, RARα strongly promoted the differentiation of T follicular helper cells followed by an enhanced germinal center response. CONCLUSIONS:9cRA signaling via RARα impacts the allergen-specific immunoglobulin response directly by the differentiation of B cells and indirectly by promoting T follicular helper cells.
Authors: Govindarajan Thangavelu; Gabriela Andrejeva; Sara Bolivar-Wagers; Sujeong Jin; Michael C Zaiken; Michael Loschi; Ethan G Aguilar; Scott N Furlan; Chrysothemis C Brown; Yu-Chi Lee; Cameron McDonald Hyman; Colby J Feser; Angela Panoskaltsis-Mortari; Keli L Hippen; Kelli P MacDonald; William J Murphy; Ivan Maillard; Geoffrey R Hill; David H Munn; Robert Zeiser; Leslie S Kean; Jeffrey C Rathmell; Hongbo Chi; Randolph J Noelle; Bruce R Blazar Journal: Cell Mol Immunol Date: 2022-05-17 Impact factor: 22.096
Authors: Govindarajan Thangavelu; Michael C Zaiken; Fathima A Mohamed; Ryan Flynn; Jing Du; Stephanie Y Rhee; Megan J Riddle; Ethan G Aguilar; Angela Panoskaltsis-Mortari; Martin E Sanders; Bruce R Blazar Journal: Front Immunol Date: 2022-03-11 Impact factor: 7.561