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IL-21 and IL-5 coordinately induce surface IgA+ cells.
Immunology Letters ( IF 3.3 ) Pub Date : 2020-05-31 , DOI: 10.1016/j.imlet.2020.05.004
Masaaki Hashiguchi 1 , Yuji Kashiwakura 1 , Yumiko Kanno 1 , Hidefumi Kojima 1 , Tetsuji Kobata 1
Affiliation  

Intestinal IgA is induced by microbes and food antigens. Peyer’s patches (PPs) are known as one of the inductive sites for intestinal IgA production. However, the precise mechanism of IgA induction is as yet unknown. IgA secretion was induced from IgD+ B cells in vitro by stimulus with lipopolysaccharide in the presence of only retinoic acid (RA) and low doses of TGF-β1. Surface IgA+ cells were effectively induced from IgD+ B cells in vitro by the mixture of RA and the cytokines TGF-β1, APRIL, IL-5 and IL-21. rIL-21 upregulated surface IgA+ but impaired the proliferation of stimulated B cells in the presence of rTGF-β1, RA and rAPRIL, in vitro. The addition of rIL-5 restored the impaired proliferation by rIL-21, resulting in the expansion of IgA+ cells. rIL-21 induced the expression of Aicda and Prdm1, and impaired Rel in IgD+ B cells. Blockade of IL-21R signaling by a neutralizing mAb in vivo led to lower frequencies of IgA+ and IgG2b+ cells and lower germinal center B cells in PPs in a homeostatic condition. Although amounts of small intestinal IgA and titers of anti-dsDNA, the major target of intestinal IgA, in these mice were not altered, anti-OVA IgA titers induced by OVA drinking in OVA-specific T-cell receptor (TCR) transgenic mice were decreased. PP-deficient TCR transgenic mice showed diminished anti-OVA IgA induction. Blockade of IL-5R signaling in vivo led to similar results with relatively weaker effects than that of IL-21R mAb administration. These results suggest that IL-21 and IL-5 play cooperative roles in surface expression of IgA in PPs.



中文翻译:

IL-21和IL-5协同诱导表面IgA +细胞。

肠道IgA由微生物和食物抗原诱导。派伊尔氏淋巴集结(PPs)被称为肠道IgA产生的诱导位点之一。但是,尚不清楚IgA诱导的确切机制。在仅视黄酸(RA)和低剂量TGF-β1的存在下,通过脂多糖刺激从IgD + B细胞诱导出IgA分泌。RA和细胞因子TGF-β1,APRIL,IL-5和IL-21的混合物可从IgD + B细胞体外有效诱导表面IgA +细胞。在存在rTGF-β1,RA和rAPRIL的情况下,rIL-21上调了表面IgA +的表达,但损害了受刺激的B细胞的增殖。rIL-5的添加恢复了rIL-21受损的增殖,导致IgA +细胞扩增。rIL-21诱导IgD + B细胞中AicdaPrdm1的表达,并削弱Rel体内中和mAb阻断IL-21R信号传导导致IgA +和IgG2b +频率降低稳态条件下PPs中的细胞和较低的生发中心B细胞。尽管在这些小鼠中小肠IgA的量和肠道IgA的主要靶标抗dsDNA的滴度没有改变,但在OVA特异性T细胞受体(TCR)转基因小鼠中通过OVA饮酒诱导的抗OVA IgA滴度仍在减少了。PP缺陷型TCR转基因小鼠显示抗OVA IgA诱导减弱。与IL-21R mAb给药相比,体内IL-5R信号传导的阻滞导致相似的结果,其作用相对较弱。这些结果表明,IL-21和IL-5在PPs中IgA的表面表达中起协同作用。

更新日期:2020-05-31
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