In Vivo Irradiation of Mice Induces Activation of Dendritic Cells.
In Vivo Irradiation of Mice Induces Activation of Dendritic Cells.
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DOI：
10.3390/ijms19082391
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发表时间：
2018-08-14
影响因子：
5.6
通讯作者：
Lumniczky K
中科院分区：
文献类型：
--
作者：
Persa E;Szatmári T;Sáfrány G;Lumniczky K
越来越清楚的是，电离辐射对某些免疫参数有积极的影响，这为放射和免疫疗法在癌症治疗中的结合打开了可能性。有功能的树突状细胞(DC)的存在是成功的抗肿瘤免疫反应的关键。虽然已经证明DC具有相对的抗辐射能力，但关于电离辐射如何改变这些细胞的功能完整性的数据却很少，而且相互矛盾。因此，我们的目的是研究全身照射对脾DC功能的影响。用0.1、0.25和2GyX射线照射C57BL/6小鼠，比较照射前后小鼠脾DC表型的变化。影响DC-T细胞相互作用的DC表面标志物增加。细胞内细胞因子直接染色测定体内细胞因子的产生。2Gy射线照射可诱导IL-1α产生增加1.6倍，而照射与脂多糖联合作用则可使IL-1 DNA产生增加3.9倍，说明照射与内毒素刺激之间具有很强的协同作用。在混合淋巴细胞反应中，研究了DC与效应T细胞和调节性T细胞的相互作用。对照动物DC对调节性T细胞的增殖有较强的诱导作用，2GyDC对效应T细胞的增殖有较强的诱导作用。通过测量DC内化和呈递卵蛋白(OVA)衍生的多肽在其主要组织相容性复合体(MHCI)分子上的能力来研究抗原的摄取和递呈。2Gy射线照射对抗原摄取或提呈无影响，低剂量照射可刺激抗原摄取，降低抗原提呈水平。综上所述，与调节性T细胞相比，大剂量体内照射可诱导T细胞共刺激标志的表达增加，促炎细胞因子的产生增加，对效应性T细胞增殖的刺激作用更强。然而，它不影响DC抗原的摄取或提呈。另一方面，低剂量辐射增加DC的抗原摄取，降低DC的抗原提呈，表明低剂量和高剂量辐射在DC中作用于不同的途径。
It is becoming clear that ionizing radiation positively influences certain immune parameters, which opens the possibility for combining radio- and immunotherapies in cancer treatment. The presence of functionally competent dendritic cells (DCs) is crucial in mounting a successful antitumor immune response. While it has been shown that DCs are relatively radioresistant, few and contradictory data are available on how ionizing radiation alters the functional integrity of these cells. Therefore, our objective was to investigate the effect of whole-body irradiation on the function of splenic DCs. C57Bl/6 mice were irradiated with 0.1, 0.25, and 2 Gy X-rays and changes in the phenotype of splenic DCs were compared to unirradiated controls. An increase was seen in DC surface markers influencing DC-T cell interactions. In vivo cytokine production was determined by direct intracellular cytokine staining. Irradiation with 2 Gy induced a 1.6-fold increase in IL-1α production, while the combination of irradiation and lipopolysaccharide (LPS) treatment induced a 3.9-fold increase, indicating a strong synergism between irradiation and LPS stimulation. Interaction of DCs with effector and regulatory T cells was investigated in a mixed lymphocyte reaction. While DCs from control animals induced stronger proliferation of regulatory T cells, DCs from animals irradiated with 2 Gy induced stronger proliferation of effector T cells. Antigen uptake and presentation was investigated by measuring the capacity of DCs to internalize and present ovalbumine (OVA)-derived peptides on their major histocompatibility complex (MHCI) molecules. Irradiation with 2 Gy did not influence antigen uptake or presentation, while low doses stimulated antigen uptake and reduced the level of antigen presentation. In conclusion, high-dose in vivo irradiation induced increased expression of T cell costimulatory markers, enhanced production of proinflammatory cytokines and a stronger stimulation of effector T cell proliferation than that of regulatory T cells. However, it did not influence DC antigen uptake or presentation. On the other hand, low-dose irradiation increased antigen uptake and lowered antigen presentation of DCs, indicating that low- and high-dose irradiation act on different pathways in DCs.
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影响因子：
4.4
作者：
Liu, F;Whitton, JL
通讯作者：
Whitton, JL
影响因子：
6.7
作者：
Balogh, Andrea;Persa, Eszter;Lumniczky, Katalin
通讯作者：
Lumniczky, Katalin
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
--
作者：
Kesminiene, A;Cardis, E
通讯作者：
Cardis, E
DOI：
10.1073/pnas.1513532112
发表时间：
2015-10-13
影响因子：
11.1
作者：
Linehan, Jonathan L.;Dileepan, Thamotharampillai;Jenkins, Marc K.
通讯作者：
Jenkins, Marc K.