Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses
Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses
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DOI：
10.4049/jimmunol.1003485
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Kumanogoh, Atsushi
中科院分区：
文献类型：
--
作者：
Nakagawa, Yukinobu;Takamatsu, Hyota;Kumanogoh, Atsushi
在寄生虫感染过程中，嗜碱性粒细胞是Th2反应的强中介。最近，嗜碱性粒细胞被显示为APC，并促进Th2偏斜和体液记忆反应。然而，调节嗜碱性粒细胞的机制仍然不清楚。在这篇文章中，我们证明了IV类信号素Sema4B通过T细胞与嗜碱性细胞的接触负向调节嗜碱性细胞的功能。在识别在免疫系统中起作用的信号素的筛查中，我们确定Sema4B在T和B细胞中表达。有趣的是，尽管淋巴细胞和树突状细胞功能正常，Sema4B(-/-)小鼠的血清IgE水平仍显著升高。重组Sema4B可显著抑制嗜碱性粒细胞产生IL-4和IL-6，并对IL-3、木瓜酶和Fc epsilon RI交联物作出反应。此外，T细胞来源的Sema4B聚集在嗜碱性粒细胞与CD4(+)T细胞的接触部位，抑制了嗜碱性粒细胞介导的Th2偏斜，表明Sema4B通过同源细胞-细胞接触来调节嗜碱性细胞的反应。此外，Sema4B(-/-)小鼠增加了嗜碱性粒细胞介导的记忆IgE的产生，这一作用可被抗Fc epsilon RIαAb消除。综上所述，这些结果表明Sema4B负性调节嗜碱性粒细胞介导的Th2和体液记忆反应。免疫学杂志，2011,186：2881-2888。
Basophils are strong mediators of Th2 responses during helminthic infections. Recently, basophils were shown to function as APCs and promote both Th2 skewing and humoral memory responses. However, the mechanisms that regulate basophils are still unclear. In this article, we show that a class IV semaphorin, Sema4B, negatively regulates basophil functions through T cell-basophil contacts. In a screen to identify semaphorins that function in the immune system, we determined that Sema4B is expressed in T and B cells. Interestingly, Sema4B(-/-) mice had considerably increased serum IgE levels despite normal lymphocyte and dendritic cell functions. Recombinant Sema4B significantly inhibited IL-4 and IL-6 production from basophils in response to various stimuli, including IL-3, papain, and Fc epsilon RI cross-linking. In addition, T cell-derived Sema4B, which accumulated at contact sites between basophils and CD4(+) T cells, suppressed basophil-mediated Th2 skewing, suggesting that Sema4B regulates basophil responses through cognate cell-cell contacts. Furthermore, Sema4B(-/-) mice had enhanced basophil-mediated memory IgE production, which was abolished by treating with an anti-Fc epsilon RI alpha Ab. Collectively, these results indicate that Sema4B negatively regulates basophil-mediated Th2 and humoral memory responses. The Journal of Immunology, 2011, 186: 2881-2888.