Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice.

Blocking IL-10 signalling at the time of immunization does not increase unwanted side effects in mice.
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免疫时阻断 IL-10 信号传导不会增加小鼠的不良副作用

DOI:
10.1186/s12865-017-0224-x
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发表时间:
2017-08-15
期刊:
影响因子:
3
通讯作者:
Wei MQ
Wei MQ
中科院分区:
医学4区
文献类型:
--
作者:
Ni G;Liao Z;Chen S;Wang T;Yuan J;Pan X;Mounsey K;Cavezza S;Liu X;Wei MQ

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背景肿瘤治疗性疫苗诱导的细胞毒性T细胞(CTL)反应是杀伤肿瘤细胞的关键。与没有IL-10信号传导阻断的免疫相比,在免疫时阻断白细胞介素10(IL-10)信号传导增加了疫苗诱导的CTL应答,并改善了对动物模型中肿瘤生长的预防。因此,这种免疫策略可能具有在临床环境中减少癌症的潜力。然而,IL-10缺乏导致肠道中的自身免疫性疾病。在免疫时阻断IL-10可能导致不希望的副作用,方法我们研究了在免疫时阻断IL-10是否会导致小鼠TC-1肿瘤模型和NOD自身免疫性疾病易感小鼠模型中的肠道炎症反应。10的产生,并且不会导致血细胞浸润到肠中,从而导致肠病理变化。此外,免疫与乳头瘤病毒样颗粒结合,同时阻断IL-10信号传导不增加自身免疫性疾病的发病率在非肥胖糖尿病(NOD)mice.ConclusionsOur结果表明,免疫与IL-10抑制剂可能有利于产生安全,有效的治疗疫苗对慢性病毒感染和癌症。
BackgroundCancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine.MethodsWe investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model.ResultsWe now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice.ConclusionsOur results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer.
在免疫时阻断 IL-10 信号传导使小鼠体内的肿瘤更容易被 T 细胞浸润。
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发表时间: 2016-02-01
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作者:
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免疫时阻断 IL-10 信号传导可抑制小鼠体内人乳头瘤病毒 16 E7 转化的 TC-1 肿瘤细胞的生长。
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