Direct comparison of canine and human immune responses using transcriptomic and functional analyses.
Direct comparison of canine and human immune responses using transcriptomic and functional analyses.
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DOI：
10.1038/s41598-023-50340-9
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发表时间：
2024-01-26
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
犬自发性癌症模型越来越多地用于评估新的联合癌症免疫治疗方法。虽然狗和人类的主要白细胞亚群和表型密切相关，但这两个物种中 T 细胞和抗原呈递细胞的功能此前尚未进行过详细比较。这些信息对于解释免疫反应数据和评估新的癌症免疫疗法对狗的潜在毒性非常重要。为了解决这个问题，我们使用体外测定来比较活化的犬和人类 T 细胞的转录组、细胞因子和增殖反应，并比较活化的巨噬细胞的反应。 T 细胞激活后的转录组分析揭示了 515 个显着上调的基因和 360 个显着下调的免疫基因的共同表达。通路分析确定了犬类和人类激活的 T 细胞之间共享的 33 条免疫通路，以及每个物种特有的 34 条免疫通路。激活的人类 T 细胞表现出明显的 Th1 偏好，而犬 T 细胞总体转录活性较低。尽管对激活的增殖反应相似，但犬 T 细胞产生的 IFN-γ 明显少于人类 T 细胞。此外，犬巨噬细胞对 IFN-γ 激活的反应明显高于人类巨噬细胞，如共刺激分子表达和 TNF-α 产生所反映。因此，这些研究揭示了狗和人类对免疫激活反应的总体广泛相似性，但也发现了重要的关键定量和定性差异，特别是在 T 细胞反应方面，在设计和评估狗的癌症免疫治疗研究时应考虑到这一点。
The canine spontaneous cancer model is increasingly utilized to evaluate new combined cancer immunotherapy approaches. While the major leukocyte subsets and phenotypes are closely related in dogs and humans, the functionality of T cells and antigen presenting cells in the two species has not been previously compared in detail. Such information would be important in interpreting immune response data and evaluating the potential toxicities of new cancer immunotherapies in dogs. To address this question, we used in vitro assays to compare the transcriptomic, cytokine, and proliferative responses of activated canine and human T cells, and also compared responses in activated macrophages. Transcriptomic analysis following T cell activation revealed shared expression of 515 significantly upregulated genes and 360 significantly downregulated immune genes. Pathway analysis identified 33 immune pathways shared between canine and human activated T cells, along with 34 immune pathways that were unique to each species. Activated human T cells exhibited a marked Th1 bias, whereas canine T cells were transcriptionally less active overall. Despite similar proliferative responses to activation, canine T cells produced significantly less IFN-γ than human T cells. Moreover, canine macrophages were significantly more responsive to activation by IFN-γ than human macrophages, as reflected by co-stimulatory molecule expression and TNF-α production. Thus, these studies revealed overall broad similarity in responses to immune activation between dogs and humans, but also uncovered important key quantitative and qualitative differences, particularly with respect to T cell responses, that should be considered in designing and evaluating cancer immunotherapy studies in dogs.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.2
作者：
通讯作者：
--
影响因子：
3
作者：
Oziolor E;Arat S;Martin M
通讯作者：
Martin M
DOI：
10.1073/pnas.1413624111
发表时间：
2014-12-02
影响因子：
11.1
作者：
Lin, Shin;Lin, Yiing;Snyder, Michael P.
通讯作者：
Snyder, Michael P.
影响因子：
2.1
作者：
Igase, Masaya;Inanaga, Sakuya;Mizuno, Takuya
通讯作者：
Mizuno, Takuya