Charité-Universitätsmedizin Berlin, Klinik für Dermatologie und Allergologie, Allergie-Centrum-Charité, Berlin, Germany; Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Klinik für Dermatologie und Allergologie, Allergie-Centrum-Charité, Berlin, Germany.
J Allergy Clin Immunol. 2018 Feb;141(2):650-658.e5. doi: 10.1016/j.jaci.2017.03.046. Epub 2017 May 17.
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.
We sought to investigate whether and to what extent 9cRA modulates the humoral immune response.
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 activated in vitro in the presence or absence of 9cRA and activation markers, and proliferation and secreted immunoglobulin levels were analyzed by using flow cytometry and ELISA.
9cRA applied together with repeated OVA challenge transiently increased specific serum IgA, IgE, and IgG 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 IgG 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.
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.
维生素 A 是适应性免疫的有力调节剂。内源性代谢产物 9-顺式视黄酸（9cRA）对过敏致敏的影响尚不清楚。
我们试图研究 9cRA 是否以及在何种程度上调节体液免疫反应。
BALB/c 小鼠用卵清蛋白（OVA）致敏和攻毒。9cRA 与抗原一起反复应用。通过 ELISA、ELISpot 和流式细胞术检测免疫球蛋白的产生和细胞分析。在存在或不存在 9cRA 的情况下，体外激活人 CD19+B 细胞，并通过流式细胞术和 ELISA 分析活化标志物、增殖和分泌免疫球蛋白水平。
与重复 OVA 攻毒一起应用 9cRA 可短暂增加特异性血清 IgA、IgE 和 IgG 血清水平（分别增加 2.0 倍和 8.9 倍）。在用 OVA 进行回忆后，添加 9cRA 可使特异性 IgE 浓度平均降低 57%，而 IgA 则强烈诱导（20 倍），IgG 水平保持不变。相应地，9cRA 组脾中存在较少的特异性 IgE-和更多的 IgA 分泌细胞。此外，9cRA 促进了特异性 B 细胞向肠系膜而不是引流淋巴结的迁移。在纯化的刺激人 B 细胞中，9cRA 明显减少 IgE 产生并增强 IgA 产生。9cRA 调节 B 细胞活化，降低 CD86 的表达并促进 IL-10 的产生。
我们的数据表明，9cRA 通过减少 IgE 反应但促进 IgA 反应来调节过敏免疫反应。因此，9cRA 可以调节过敏免疫反应向非 IgE 状态。
