bPorcine epidemic diarrhea has become pandemic in the Asian pig-breeding industry, causing significant economic loss. In the present study, 11 complete genomes of porcine epidemic diarrhea virus (PEDV) field isolates from China were determined and analyzed. Frequently occurring mutations were observed, which suggested that full understanding of the genomic and epidemiological characteristics is critical in the fight against PEDV epidemics. Comparative analysis of 49 available genomes clustered the PEDV strains into pandemic (PX) and classical (CX) groups and identified four hypervariable regions (V1 to V4). Further study indicated key roles for the spike (S) gene and the V2 region in distinguishing between the PX and CX groups and for studying genetic evolution. Genotyping and phylogeny-based geographical dissection based on 219 S genes revealed the complexity and severity of PEDV epidemics in Asia. Many subgroups have formed, with a wide array of mutations in different countries, leading to the outbreak of PEDV in Asia. Spatiotemporal reconstruction based on the analysis suggested that the pandemic group strains originated from South Korea and then extended into Japan, Thailand, and China. However, the novel pandemic strains in South Korea that appeared after 2013 may have originated from a Chinese variant. Thus, the serious PED epidemics in China and South Korea in recent years were caused by the complex subgroups of PEDV. The data in this study have important implications for understanding the ongoing PEDV outbreaks in Asia and will guide future efforts to effectively prevent and control PEDV.
Interleukin-17E (IL-17E) belongs to a novel family of cytokines that possess significant homology to IL-17. IL-17E has potent inflammatory effects in vitro and in vivo. Overexpression of IL-17E in mice results in a T helper-2 (Th2)-type immune response, which includes the expansion of eosinophils through the production of IL-5, and elevated gene expression of IL-4 and IL-13 in multiple tissues. In this study, we show that IL-17E has antitumor activity in vivo, a previously unrecognized function of IL-17E. Antitumor efficacy of IL-17E was examined in a variety of human tumor xenograft models, including melanoma, breast, lung, colon, and pancreatic cancers. Injection of recombinant IL-17E every other day resulted in significant antitumor activity in these tumor models. In addition, the combination of IL-17E with chemotherapy or immunotherapy agents showed an enhanced antitumor efficacy in human tumor xenograft models in mice as compared to either agent alone. Antitumor activity was demonstrated using different routes of administration, including intraperitoneal, intravenous, and subcutaneous injection. Anticancer activity was shown for both mouse and human forms of IL-17E, which have a high degree of sequence identity. Tumor-bearing mice treated with IL-17E showed a significant increase in serum levels of IL-5 and increased numbers of eosinophils in peripheral blood compared to the control group. Spleens isolated from IL-17E-treated mice showed a significant increase in eosinophils that correlated with antitumor activity of IL-17E in a dose-response manner. Finally, we demonstrate that B cells are necessary for IL-17E-mediated antitumor activity and that IL-17E was found to activate signaling pathways in B cells in vitro. Taken together, these data demonstrate that IL-17E has antitumor activity in vivo, and support further investigation of the potential clinical use of IL-17E as an anticancer agent.
Immunoregulation in the testis is characterized by a balance between immuno-suppression (or immune privilege) and the ability to react to infections and inflammation. In this review, we analyze the phenotypes of the various immune cell subtypes present in the testis, and how their functions change between homeostatic and inflammatory conditions. Starting with testicular macrophages, we explore how this heterogeneous population is shaped by the testicular microenvironment to ensure immune privilege. We then describe how dendritic cells exhibit a tolerogenic status under normal conditions, but proliferate, mature and then stimulate effector T-cell expansion under inflammatory conditions. Finally, we outline the two T-cell populations in the testis: CD4
+
/CD8
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αβ T cells and CD4
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/CD8
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Foxp3
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regulatory T cells and describe the distribution and function of mast cells. All these cells help modulate innate immunity and regulate the immune response. By improving our understanding of immune cell behavior in the testis under normal and inflammatory conditions, we will be better placed to evaluate testis impairment due to immune mechanisms in affected patients.
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