Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 31
·4854-4866
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IF 5.047
Xuanjin Wu,Yang Li,Xiguang Chen,Zhongzheng Zhou,Jianhui Pang,Xin Luo,Ming Kong
The efficient delivery of vaccines to draining lymph nodes and the induction of robust local immune responses are crucial for immunotherapy. Transdermal administration has been evidenced to facilitate the delivery of ingredients to lymph nodes. In this study, transfersomes with opposite surface charges were applied for antigen encapsulation and these were integrated with dissolving microneedles to investigate their effects on immune responses via transdermal immunization. The microneedles were easily inserted into mouse skin and achieved the local release of nanovaccines into the dermis through dissolution. Although anionic nanovaccines promoted cellular uptake via DC2.4, cationic nanovaccines exhibited stronger escape capacities from endocytic compartments, facilitating antigen processing via an MHC-I presentation pathway, and formed larger accumulations in lymph nodes. Compared with their anionic counterparts, the cationic nanovaccines more efficiently activated DC maturation and induced Th1 immunity; this was suggested by the significantly increased IgG2a/IgG1 ratio and elevated cytokine secretion from Th1 cells, without an enhancement in the Th2 response. Such an enhanced Th1 antigen-specific immune response in lymph nodes via a transdermal vaccine delivery platform is beneficial for potential immunotherapy approaches.
研究领域:
免疫学
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药学
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纳米技术
·
疫苗递送系统
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2024
·
IF 10.8
Xiuxiu Yao,Wendi Huo,Yuchen Wang,Dongfang Xia,Yan Chen,Yuhua Tang,Huayong Tang,Wenjiang Yang,Yu Liu,Jingquan Xue,Qing Yuan,Xueyun Gao,Kai Cao
The presence of low-dose radiation (LDR) in the environment has become more prevalent. However, the effect of LDR exposure on the immune system remains elusive. Here, we interestingly found that LDR specifically elevated the percentage of CD4+IFNγ+ Th1 splenocytes, both in vitro and in vivo, without affecting the percentage of CD8+IFNγ+ Tc1 cells and regulatory T cells. A similar phenomenon was found in T cells from peripheral blood. Mechanistically, we found that LDR can induce mitochondrial damage, which stimulated the STING signaling pathway, leading to the enhanced expression of T-bet, the master transcriptional factor of Th1-cell differentiation. The specific STING signal inhibitor can abrogate the effect of LDR on Th1 differentiation, confirming the central role of the STING pathway. To further validate the immunoregulatory role of LDR, we exposed mice with whole body LDR and evaluated if LDR could protect mice against triple-negative breast cancer through enhanced antitumor immunity. As expected, LDR significantly delayed tumor development and promoted cell death. Meanwhile, LDR resulted in increased tumor-infiltrating Th1 cells, while the proportion of Tc1 and Treg cells remained unchanged. Furthermore, the infiltration of antitumor macrophages was also increased. In summary, we revealed that environmental LDR could specifically regulate Th1 T-cell activities, providing critical information for the potential application of LDR in both clinical and nonclinical settings.
研究领域:
免疫学
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肿瘤学
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放射生物学
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DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
·
2024
·
IF 3.6
Zhu Yiqiang,Zhou Lu,Mo Lengshan,Hong Cansheng,Pan Lingxia,Lin Jie,Qi Yanwei,Tan Simin,Qian Manhongtian,Hu Tengfei,Zhao Yi,Qiu Huaina,Lin Peibin,Ma Xiancai,Yang Quan
Myeloid-derived suppressor cells (MDSCs), the negative immune regulators, have been demonstrated to be involved in immune responses to a variety of pathological conditions, such as tumors, chronic inflammation, and infectious diseases. However, the roles and mechanisms underlying the expansion of MDSCs in malaria remain unclear. In this study, the phenotypic and functional characteristics of splenic MDSCs during Plasmodium yoelii NSM infection are described. Furthermore, we provide compelling evidence that the sera from P. yoelii–infected C57BL/6 mice containing excess IL-6 and granulocyte-macrophage colony-stimulating factor promote the accumulation of MDSCs by inducing Bcl2 expression. Serum-induced MDSCs exert more potent suppressive effects on T cell responses than control MDSCs within both in vivo P. yoelii infection and in vitro serum-treated bone marrow cells experiments. Serum treatment increases the MDSC inhibitory effect, which is dependent on Arg1 expression. Moreover, mechanistic studies reveal that the serum effects are mediated by JAK/STAT3 signaling. By inhibiting STAT3 phosphorylation with the JAK inhibitor JSI-124, effects of serum on MDSCs are almost eliminated. In vivo depletion of MDSCs with anti–Gr-1 or 5-fluorouracil significantly reduces the parasitemia and promotes Th1 immune response in P. yoelii–infected C57BL/6 mice by upregulating IFN-γ expression. In summary, this study indicates that P. yoelii infection facilitates the accumulation and function of MDSCs by upregulating the expression of Bcl2 and Arg1 via JAK/STAT3 signaling pathway in vivo and in vitro. Manipulating the JAK/STAT3 signaling pathway or depleting MDSCs could be promising therapeutic interventions to treat malaria.
研究领域:
免疫学
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传染病学
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细胞生物学
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疟疾
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产品关联
DOI
PubMed
高影响因子
Vaccines
·
2021
·Vol. 9
·期 7
·786
·
IF 4.422
Linpei Guo,Hui Xie,Zheng Zhang,Zhun Wang,Shuanghe Peng,Yuanjie Niu,Zhiqun Shang
(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine withMycobacterium tuberculosisAg85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1186-193), Ag85B-3×STEAP1186-193. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3+cells and fewer FOXP3+cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund’s adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.Keywords:Ag85B;Mycobacteriumtuberculosis;STEAP1;six-transmembrane epithelial antigen of the prostate 1;immune response;prostate cancer;castration-resistant prostate cancer (CRPC)
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症免疫疗法
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）