Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance.
Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance.
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DOI：
10.1111/ajt.15163
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发表时间：
2019-04
期刊：
影响因子：
--
通讯作者：
Gelman AE
中科院分区：
文献类型：
--
作者：
Scozzi D;Wang X;Liao F;Liu Z;Zhu J;Pugh K;Ibrahim M;Hsiao HM;Miller MJ;Yizhan G;Mohanakumar T;Krupnick AS;Kreisel D;Gelman AE
中性粒细胞胞外陷阱(Net)可加重急性肺损伤，包括肺移植后。DNase-1对Net的破坏可以帮助恢复肺功能，但是否会对同种异体移植的耐受性产生影响仍不清楚。采用活体双光子显微镜观察DNase-1对小鼠原位肺移植缺血再灌注损伤后NETs的影响。尽管DNase-1治疗会迅速降解移植物内的Net，但Net片段的释放会导致浸润性的CD4+T细胞与供体来源的抗原提呈细胞之间的长时间相互作用。DNase-1产生的Net片段还通过激活Toll样受体(TLR)-髓样分化初级反应88(MyD88)信号通路，促进人肺泡巨噬细胞炎性细胞因子的产生和同种抗原特异性CD4+T细胞的初始树突状细胞增殖。此外，与由于中性粒细胞特异性去除精氨酸脱亚胺酶4(PAD4)而导致净生成不足的同种异体移植受体相比，野生型受体给予DNase-1促进了对同种和自身抗原的识别，并通过MyD88依赖的途径阻止了免疫抑制介导的同种异体肺移植接受。综上所述，这些数据表明，网络碎片的快速催化释放促进了防止肺移植耐受的先天免疫反应。
Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs the consequential release of NET fragments induces prolonged interactions between infiltrating CD4+ T cells and donor-derived antigen presenting cells. DNAse-1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen-specific CD4+ T cell proliferation through activating Toll-like receptor (TLR) - Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil-specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse-1 administration to wildtype recipients promotes the recognition of allo- and self-antigens and prevents immunosuppression-mediated lung allograft acceptance through a MyD88-dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
影响因子：
82.9
作者：
Liang J;Zhang Y;Xie T;Liu N;Chen H;Geng Y;Kurkciyan A;Mena JM;Stripp BR;Jiang D;Noble PW
通讯作者：
Noble PW
影响因子：
14.8
作者：
Krupnick, Alexander S.;Lin, Xue;Li, Wenjun;Okazaki, Mikio;Lai, Jiaming;Sugimoto, Seiichiro;Richardson, Steven B.;Kornfeld, Christopher G.;Garbow, Joel R.;Patterson, G. Alexander;Gelman, Andrew E.;Kreisel, Daniel
通讯作者：
Kreisel, Daniel
DOI：
10.1165/rcmb.2011-0380oc
发表时间：
2012-07-01
影响因子：
6.4
作者：
Dubois, Alice V.;Gauthier, Alexandre;Attucci, Sylvie
通讯作者：
Attucci, Sylvie
DOI：
10.1073/pnas.1510760112
发表时间：
2015-11-10
影响因子：
11.1
作者：
Hu, Wei;Jain, Aakanksha;Pasare, Chandrashekhar
通讯作者：
Pasare, Chandrashekhar