Vitamin A controls the allergic response through T follicular helper cell as well as plasmablast differentiation.

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.