Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.
Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.
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DOI：
10.1038/srep18738
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发表时间：
2016-01-06
影响因子：
4.6
通讯作者：
Adachi T
中科院分区：
文献类型：
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作者：
Yoshikawa S;Usami T;Kikuta J;Ishii M;Sasano T;Sugiyama K;Furukawa T;Nakasho E;Takayanagi H;Tedder TF;Karasuyama H;Miyawaki A;Adachi T
钙离子（Ca 2+）信号是通过免疫受体介导的典型现象，例如B细胞抗原受体（BCR），并且其对于它们的生物活性是重要的。为了分析免疫受体的信号传导及其体内动力学，我们基于Cre/loxP系统（YC 3.60flox），使用基于Föster/荧光共振能量转移（FRET）的Ca 2+指示剂黄色cameleon 3.60（YC 3.60）生成了稳定的转基因小鼠。我们成功地获得了在免疫或神经细胞中具有特异性YC3.60表达的小鼠以及具有该指示物的普遍表达的小鼠。我们建立了包括骨髓在内的淋巴组织的五维（5D）（x，y，z，时间和Ca 2+）活体成像。此外，在自身免疫易感模型中，CD 22 −/−和C57 BL/6-淋巴细胞增殖（lpr）/lpr小鼠的Ca 2+通量增加，尽管它们不会诱导自身免疫性疾病。淋巴细胞中Ca 2+信号的活体成像可以改善模型动物中自身免疫性疾病风险的评估。
Calcium ion (Ca2+) signaling is a typical phenomenon mediated through immune receptors, such as the B-cell antigen receptor (BCR), and it is important for their biological activities. To analyze the signaling of immune receptors together with their in vivo dynamics, we generated stable transgenic mice with the Föster/fluorescence resonance energy transfer (FRET)-based Ca2+ indicator yellow cameleon 3.60 (YC3.60), based on the Cre/loxP system (YC3.60flox). We successfully obtained mice with specific YC3.60 expression in immune or nerve cells as well as mice with ubiquitous expression of this indicator. We established five-dimensional (5D) (x, y, z, time, and Ca2+) intravital imaging of lymphoid tissues, including the bone marrow. Furthermore, in autoimmune-prone models, the CD22−/− and C57BL/6- lymphoproliferation (lpr)/lpr mouse, Ca2+ fluxes were augmented, although they did not induce autoimmune disease. Intravital imaging of Ca2+ signals in lymphocytes may improve assessment of the risk of autoimmune diseases in model animals.