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Τετάρτη 17 Μαΐου 2017

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

Publication date: Available online 17 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Guido Heine, Tim Hollstein, Sandra Treptow, Andreas Radbruch, Margitta Worm
BackgroundVitamin A is a potent regulator of adaptive immunity. The impact of the endogenous metabolite 9-cis retinoic acid (9cRA) on allergic sensitization is unknown.ObjectiveTo investigate whether and to what extent 9cRA modulates the humoral immune response.MethodsBALB/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 ELISA, ELISPOTs and flow-cytometry. Human CD19+ B cells were activated in vitro in the presence or absence of 9cRA and activation markers, proliferation and secreted Ig were analyzed by flow-cytometry and ELISA.Results9cRA applied together with repeated OVA challenges transiently increased specific serum IgA, IgE and IgG1 serum levels (2.0-8.9-fold). After OVA recall, specific IgE concentrations were reduced by a mean of 57% after adding 9cRA, while IgA was strongly induced (20-fold) and IgG1 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 the 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.ConclusionsOur 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 towards a non-IgE condition.

Graphical abstract

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Teaser

The physiological vitamin A receptor agonist 9-cis retinoic acid contributes to the control of type I allergic immune reactions in mice and humans by reducing IgE and inducing IgA.


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