9-cis retinoic acid modulates the type I allergic immune response

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Background:Vitamin A is a potent regulator of adaptive immunity. The effect of the endogenous metabolite 9-cis retinoic acid (9cRA) on allergic sensitization is unknown.Objective:We sought to investigate whether and to what extent 9cRA modulates the humoral immune response.Methods:BALB/c mice were sensitized and challenged with ovalbumin (OVA). 9cRA was applied repeatedly together with the antigen. Immunoglobulin production and cellular analysis were performed by using ELISA, ELISpot, and flow cytometry. Human CD19+ B cells were activatedin vitroin the presence or absence of 9cRA and activation markers, and proliferation and secreted immunoglobulin levels were analyzed by using flow cytometry and ELISA.Results:9cRA applied together with repeated OVA challenge transiently increased specific serum IgA, IgE, and IgG1 serum levels (2.0- and 8.9-fold). After OVA recall, specific IgE concentrations were reduced by a mean of 57% after adding 9cRA, whereas IgA was strongly induced (20-fold), and IgG1 levels remained unchanged. Correspondingly, less specific IgE- and more IgA-secreting cells resided in the spleen in the 9cRA groups. Additionally, 9cRA promoted the migration of specific B cells to the mesenteric but not draining lymph nodes. In purified stimulated human B cells, 9cRA markedly reduced IgE production and enhanced IgA production. B-cell activation was modulated by 9cRA, reducing the expression of CD86 and promoting IL-10.Conclusions:Our data indicate that 9cRA modulates the allergic immune response by reducing the IgE response but promoting the IgA response. Thus 9cRA can modulate the allergic immune response toward a non-IgE condition.Graphical abstract

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