Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model.
Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model.
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预敏化心脏移植模型中供体 IL-6 缺乏对先天免疫的改变
DOI：
10.1371/journal.pone.0077559
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gong W
中科院分区：
文献类型：
--
作者：
Ge F;Yuan S;Su L;Shen Z;He A;Huang T;Gong W
将IL-6缺陷供者植入野生型受体可通过T细胞谱系，特别是非致敏移植宿主中的调节性T细胞(Tregs)显着提高同种异体移植物存活率。然而，它对先天免疫反应的影响仍不确定。结果表明，供者IL-6缺乏显著增加了CD11b+Gr1+髓系来源抑制细胞两个亚群CD11b+Gr1-low和CD11b+Gr1-int在移植物中的渗透，具有较强的免疫抑制活性。受者脾中CD11b+Gr1-低频率显著升高，CD11b+Gr1-高频率和CD4-CD8-NK1.1+细胞频率显著降低。出乎意料的是，供者IL-6缺乏并不能显著降低巨噬细胞的频率，无论是在宿主的脾还是移植物中。综上所述，抑制天然免疫效应细胞和增强调节性MDSCs的活性有助于阻断IL-6信号通路而诱导耐受。IL-6靶向的新机制可能为预防预致敏移植受者加速排斥反应的临床治疗应用提供参考。
Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1-low and CD11b+Gr1-int with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1-low frequency and a significant decrease of the frequency of CD11b+Gr1-high and CD4-CD8-NK1.1+ cells in the recipient’s spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host’s spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.
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影响因子：
64.8
作者：
Oka, Takafumi;Hikoso, Shungo;Yamaguchi, Osamu;Taneike, Manabu;Takeda, Toshihiro;Tamai, Takahito;Oyabu, Jota;Murakawa, Tomokazu;Nakayama, Hiroyuki;Nishida, Kazuhiko;Akira, Shizuo;Yamamoto, Akitsugu;Komuro, Issei;Otsu, Kinya
通讯作者：
Otsu, Kinya
影响因子：
7.8
作者：
Oberbarnscheidt MH;Zecher D;Lakkis FG
通讯作者：
Lakkis FG
DOI：
10.4049/jimmunol.1100766
发表时间：
2011-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Booth AJ;Grabauskiene S;Wood SC;Lu G;Burrell BE;Bishop DK
通讯作者：
Bishop DK
DOI：
10.1126/science.1198687
发表时间：
2011-01-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Vivier E;Raulet DH;Moretta A;Caligiuri MA;Zitvogel L;Lanier LL;Yokoyama WM;Ugolini S
通讯作者：
Ugolini S
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R