Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia.
Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia.
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DOI：
10.3389/fimmu.2023.1278397
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
树突状细胞（dc），专业抗原呈递细胞，作为免疫系统的哨兵。dc通过向B淋巴细胞和T淋巴细胞呈递抗原肽来启动和微调适应性免疫反应，从而对癌症和病原体产生有效的免疫反应。然而，缺氧是一种以不同组织中的低氧（O2）张力为特征的状态，它显著影响DC功能，包括抗原摄取、激活和成熟、迁移以及t细胞的启动和增殖。在本研究中，我们使用O2释放生物材料（O2- cryoglels）来研究局部O2供应对人类DC表型和功能的影响。我们的研究结果表明，在缺氧条件下，o2低温冰箱可以有效地减轻DC暴露于缺氧。此外，O2-低温冰箱通过O2释放和透明质酸（HA）介导的机制抵消缺氧诱导的dc中抗原摄取和迁移活性的抑制。此外，o2低温保存和恢复DC成熟和共刺激标志物，包括HLA-DR、CD86和CD40，以及促炎细胞因子在缺氧条件下的分泌。最后，我们的研究结果表明，从低温冰箱中释放的补充O2保存了dc介导的T细胞启动，最终导致异体CD3+ T细胞的激活和增殖。这项工作强调了局部氧合作为一种强大的免疫调节剂的潜力，可以改善DC在缺氧中的激活和功能，为癌症和传染病的治疗提供新的途径。
Dendritic cells (DCs), professional antigen-presenting cells, function as sentinels of the immune system. DCs initiate and fine-tune adaptive immune responses by presenting antigenic peptides to B and T lymphocytes to mount an effective immune response against cancer and pathogens. However, hypoxia, a condition characterized by low oxygen (O2) tension in different tissues, significantly impacts DC functions, including antigen uptake, activation and maturation, migration, as well as T-cell priming and proliferation. In this study, we employed O2-releasing biomaterials (O2-cryogels) to study the effect of localized O2 supply on human DC phenotype and functions. Our results indicate that O2-cryogels effectively mitigate DC exposure to hypoxia under hypoxic conditions. Additionally, O2-cryogels counteract hypoxia-induced inhibition of antigen uptake and migratory activity in DCs through O2 release and hyaluronic acid (HA) mediated mechanisms. Furthermore, O2-cryogels preserve and restore DC maturation and co-stimulation markers, including HLA-DR, CD86, and CD40, along with the secretion of proinflammatory cytokines in hypoxic conditions. Finally, our findings demonstrate that the supplemental O2 released from the cryogels preserves DC-mediated T-cell priming, ultimately leading to the activation and proliferation of allogeneic CD3+ T cells. This work emphasizes the potential of local oxygenation as a powerful immunomodulatory agent to improve DC activation and functions in hypoxia, offering new approaches for cancer and infectious disease treatments.
影响因子：
5.4
作者：
Lin CA;Ho HM;Venkatesan P;Huang CY;Cheng YJ;Lin YH;Lin HY;Chen TY;Huang MH;Lai PS
通讯作者：
Lai PS
影响因子：
3.7
作者：
Spirig R;Djafarzadeh S;Regueira T;Shaw SG;von Garnier C;Takala J;Jakob SM;Rieben R;Lepper PM
通讯作者：
Lepper PM