白细胞介素2调节人嗜碱性细胞的活化
2019/12/09
摘要
嗜碱细胞是过敏性疾病和抗寄生虫免疫应答的重要效应细胞。许多激活因子包括白细胞介素3 (IL-3)和IgE已被确定在调节人类嗜碱性细胞表达介质如组胺和白三烯C4 (LTC4)和包括IL-4和IL-13在内的细胞因子。人类嗜碱性细胞表达高水平的IL-2受体。然而，IL-2通路在嗜碱性细胞中的作用仍不清楚。在此，我们发现IL-2在体外诱导人嗜碱性细胞活化，表达多种炎症细胞因子和趋化因子，包括IL-5、IL-13、GM-CSF和CCL -17。IL-2的这种作用通过使用独创性途径分析的上游调节因子分析得到证实。值得注意的是，在人嗜碱性细胞中，IL-5是第一次被发现是由IL-2而不是IL-3或抗IgE引起的。对大疱性类天疱疮和湿疹皮肤标本的免疫荧光分析显示，皮肤病变中浸润的嗜碱性细胞广泛表达IL-5和GM-CSF。总之，我们的发现揭示了IL-2作为人类嗜碱性细胞的一种新的调节因子。这增加了一个新的层面来支持嗜碱细胞在过敏性疾病中的重要性。
Zhao S, Tang Y, Hong L, Xu M, Pan S, Zhen K, Tang R, Zhai X, Shi Z, Wang H.
Abstract
Basophils are important effector cells in allergic disorders and anti-parasitic immune response. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identified that IL-2 induced the activation of human basophils in vitro to express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. This effect by IL-2 is confirmed by an upstream regulator analysis using Ingenuity pathway analysis. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be induced by IL-2 in human basophils rather than IL-3 or anti-IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely expressed IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils. This adds a new layer to support the importance of basophils in allergic disorders.
嗜碱细胞是过敏性疾病和抗寄生虫免疫应答的重要效应细胞。许多激活因子包括白细胞介素3 (IL-3)和IgE已被确定在调节人类嗜碱性细胞表达介质如组胺和白三烯C4 (LTC4)和包括IL-4和IL-13在内的细胞因子。人类嗜碱性细胞表达高水平的IL-2受体。然而，IL-2通路在嗜碱性细胞中的作用仍不清楚。在此，我们发现IL-2在体外诱导人嗜碱性细胞活化，表达多种炎症细胞因子和趋化因子，包括IL-5、IL-13、GM-CSF和CCL -17。IL-2的这种作用通过使用独创性途径分析的上游调节因子分析得到证实。值得注意的是，在人嗜碱性细胞中，IL-5是第一次被发现是由IL-2而不是IL-3或抗IgE引起的。对大疱性类天疱疮和湿疹皮肤标本的免疫荧光分析显示，皮肤病变中浸润的嗜碱性细胞广泛表达IL-5和GM-CSF。总之，我们的发现揭示了IL-2作为人类嗜碱性细胞的一种新的调节因子。这增加了一个新的层面来支持嗜碱细胞在过敏性疾病中的重要性。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Cytokine. 2019 Nov 26;127:154934. doi: 10.1016/j.cyto.2019.154934. )
(Cytokine. 2019 Nov 26;127:154934. doi: 10.1016/j.cyto.2019.154934. )
Interleukin 2 regulates the activation of human basophils.
Zhao S, Tang Y, Hong L, Xu M, Pan S, Zhen K, Tang R, Zhai X, Shi Z, Wang H.
Abstract
Basophils are important effector cells in allergic disorders and anti-parasitic immune response. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identified that IL-2 induced the activation of human basophils in vitro to express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. This effect by IL-2 is confirmed by an upstream regulator analysis using Ingenuity pathway analysis. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be induced by IL-2 in human basophils rather than IL-3 or anti-IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely expressed IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils. This adds a new layer to support the importance of basophils in allergic disorders.
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