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.
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