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

Vitamin A controls the allergic response through T follicular helper cell as well as plasmablast differentiation
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维生素 A 通过滤泡辅助 T 细胞和浆母细胞分化控制过敏反应

DOI:
10.1111/all.14581
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发表时间:
2021
期刊:
影响因子:
12.4
通讯作者:
Heine G
Heine G
中科院分区:
医学1区
文献类型:
--
作者:
Scholz J;Kuhrau J;Heinrich F;Heinz GA;Hutloff A;Worm M;Heine G

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背景维生素A调节适应性免疫反应和I型变态反应的调节作用进行了讨论。Objective. Objective确定维生素A应答的特异性淋巴细胞反应in vivo.MethodsAntigen‐specific B和T淋巴细胞在过继转移气道炎症小鼠模型中对9‐cis retinoic acid(9 cRA)的应答以及淋巴细胞特异性基因靶向受体RARα后进行分析。流式细胞术,定量PCR,下一代测序,和特定的IG-ELISA被用来表征cells functional.ResultsSystemic 9 cRA深刻地增强了特定的伊加分泌B-细胞的频率在肺组织和血清伊加,同时降低血清IgE浓度。RARα在抗原特异性B细胞中的过表达以生殖中心B细胞为代价促进了向浆母细胞的分化。在抗原特异性T细胞中,RARα强烈促进T滤泡辅助细胞的分化,随后增强生发中心反应。结论RARα介导的9 cRA信号直接通过B细胞的分化影响变应原特异性免疫球蛋白反应,间接通过促进T滤泡辅助细胞的分化影响变应原特异性免疫球蛋白反应。
BackgroundVitamin A regulates the adaptive immune response and a modulatory impact on type I allergy is discussed. The cellular mechanisms are largely unknown.ObjectiveTo determine the vitamin A‐responding specific lymphocyte reaction in vivo.MethodsAntigen‐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.ResultsSystemic 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.Conclusions9cRA 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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