血红素加氧酶-1的上调会导致未成熟树突状细胞具有更强效和持久的免疫调节特性，并在严格的小鼠心脏同种异体移植模型中促进植入。,Frontiers in Immunology

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血红素加氧酶-1的上调会导致未成熟树突状细胞具有更强效和持久的免疫调节特性，并在严格的小鼠心脏同种异体移植模型中促进植入。
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2018-07-18 , DOI: 10.3389/fimmu.2018.01515
Yue Zhao _{1,

2,

3} , Yu Jia _{1,

4} , Lu Wang _{1,

5,

6} , Song Chen _{1,

5,

6} , Xia Huang _{1,

5,

6} , Bingyang Xu ₁ , Guangyuan Zhao ₁ , Ying Xiang _{1,

5,

6} , Jun Yang _{1,

5,

6} , Gang Chen _{1,

5,

6}

Affiliation

血红素加氧酶-1（HO-1）对于未成熟树突状细胞（imDC）抑制T细胞反应的能力至关重要。HO-1高表达的诱导可能显着提高imDCs的致耐受能力。在这里，我们从BALB / c小鼠中以低剂量的GM-CSF和IL-4产生了骨髓来源的DC（BMDC）。获得粘附的BMDC作为imDC。imDCs（HO-1hi-imDCs）中HO-1的上调是通过钴原卟啉处理实现的。HO-1hi-imDCs被证明比传统imDCs具有更高的抗成熟性，并且具有增强的抑制抗CD3 / CD28抗体刺激的同种异体T细胞增殖的能力。当在严格的小鼠心脏同种异体移植模型中进行供体来源的DC过继转移时，HO-1hi imDCs观察到的移植物延长程度优于常规imDCs。与未治疗的imDC组相比，HO-1hi imDC输血组中心脏同种异体移植受者的T细胞活化和增殖受到更强的抑制。此外，在过继转移后，供体HO-1hi imDCs能够维持高HO-1表达状态，并且在接受者脾脏中的存活时间比未处理的imDCs长。体外产生的HO-1hi imDCs具有增强的致耐受能力，可在体内和体外调节同种免疫反应，因此可提供诱导抗原耐受的新型抗原特异性且具有成本效益的策略。供体HO-1hi imDCs能够维持高HO-1表达状态，并且在过继移植后，在接受者脾脏中的存活时间比未处理的imDCs长。体外产生的HO-1hi imDCs具有增强的致耐受能力，可在体内和体外调节同种免疫反应，因此可提供诱导抗原耐受的新型抗原特异性且具有成本效益的策略。供体HO-1hi imDCs能够维持高HO-1表达状态，并且在过继移植后，在接受者脾脏中的存活时间比未处理的imDCs长。体外产生的HO-1hi imDCs具有增强的致耐受能力，可在体内和体外调节同种免疫反应，因此可提供诱导抗原耐受的新型抗原特异性且具有成本效益的策略。

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Upregulation of Heme Oxygenase-1 Endues Immature Dendritic Cells With More Potent and Durable Immunoregulatory Properties and Promotes Engraftment in a Stringent Mouse Cardiac Allotransplant Model.

Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi-imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi-imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies. When donor-derived DC adoptive transfer was performed in a stringent mouse cardiac allotransplant model, the extent of graft prolongation observed with HO-1hi imDCs was superior to that obtained with conventional imDCs. T-cell activation and proliferation in cardiac allograft recipients was more strongly suppressed in the HO-1hi imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1hi imDCs were able to maintain a status of high HO-1 expression and survived longer in the recipient spleens than did untreated imDCs after adoptive transfer. In vitro-generated HO-1hi imDCs had an enhanced tolerogenic capacity to modulate alloimmune responses both in vitro and in vivo, and thus may offer a novel antigen-specific and cost-effective strategy to induce transplant tolerance.

更新日期：2019-11-01

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