Donor plasmacytoid dendritic cells modulate effector and regulatory T cell responses in mouse spontaneous liver transplant tolerance.
Donor plasmacytoid dendritic cells modulate effector and regulatory T cell responses in mouse spontaneous liver transplant tolerance.
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供体浆细胞样树突状细胞调节小鼠自发性肝移植耐受中的效应和调节性T细胞反应。
DOI：
10.1111/ajt.16412
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Thomson AW
中科院分区：
文献类型：
--
作者：
Nakano R;Yoshida O;Kimura S;Nakao T;Yokota S;Ono Y;Minervini MI;Geller DA;Thomson AW
我们评估了供体肝脏非常规浆细胞样树突状细胞（pDC）在完全MHC错配（C57 BL/6（H2 b）至C3 H（H2k））小鼠模型中自发性肝移植耐受中的作用。与脾脏pDC相比，肝脏pDC在稳态和Toll样受体9连接后表达更高水平的12 kDa DNA X活化蛋白及其共受体，髓样细胞表达的触发受体2，以及更高的程序性死亡配体1（PD-L1）：共刺激CD 80/CD 86的比例。此外，肝pDC有效地抑制同种异体CD 4+和CD 8 + T细胞增殖反应。与未处理的供体肝脏或无限期存活的pDC耗尽的同基因供体肝脏相比，pDC耗尽的肝脏的存活率要差得多（中位存活时间：25天）。与未处理肝脏的受体相比，给予pDC缺失的同种异体肝脏的小鼠移植物和肠系膜淋巴结中叉头盒p3（FoxP 3）+调节性T细胞的数量显着减少。移植物浸润的CD 8 + T细胞与耗尽的表型（程序性细胞死亡蛋白1+，T细胞免疫球蛋白和粘蛋白结构域蛋白3+）也减少了pDC耗尽的肝脏受体。PD 1-PD-L1通路阻断逆转了耗竭T细胞的减少。这些新的观察结果将肝间质pDC的免疫调节功能、同种异体反应性T细胞耗竭和自发性肝移植耐受联系起来。
We assessed the role of donor liver non-conventional plasmacytoid dendritic cells (pDCs) in spontaneous liver transplant tolerance in a fully MHC-mismatched (C57BL/6 (H2b) to C3H (H2k)) mouse model. Compared with spleen pDCs, liver pDCs expressed higher levels of DNAX-activating protein of 12 kDa and its co-receptor, triggering receptor expressed by myeloid cells 2, and higher ratios of programed death ligand-1 (PD-L1):costimulatory CD80/CD86 in the steady state and after Toll-like receptor 9 ligation. Moreover, liver pDCs potently suppressed allogeneic CD4+ and CD8+ T cell proliferative responses. Survival of pDC-depleted livers was much poorer (median survival time: 25 days) than that of either untreated donor livers or pDC-depleted syngeneic donor livers that survived indefinitely. Numbers of forkhead box p3 (FoxP3)+ regulatory T cells in grafts and mesenteric lymph nodes of mice given pDC-depleted allogeneic livers were reduced significantly compared with those in recipients of untreated livers. Graft-infiltrating CD8+ T cells with an exhausted phenotype (programed cell death protein 1+, T cell immunoglobulin and mucin domain-containing protein 3+) were also reduced in recipients of pDC-depleted livers. PD1-PD-L1 pathway blockade reversed the reduction in exhausted T cells. These novel observations link immunoregulatory functions of liver interstitial pDCs, alloreactive T cell exhaustion, and spontaneous liver transplant tolerance.
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DOI：
10.1111/j.1600-6143.2009.02859.x
发表时间：
2010-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Morita M;Fujino M;Jiang G;Kitazawa Y;Xie L;Azuma M;Yagita H;Nagao S;Sugioka A;Kurosawa Y;Takahara S;Fung J;Qian S;Lu L;Li XK
通讯作者：
Li XK
DOI：
10.4049/jimmunol.0900582
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castellaneta A;Sumpter TL;Chen L;Tokita D;Thomson AW
通讯作者：
Thomson AW
影响因子：
32.4
作者：
Goubier, Anne;Dubois, Bertrand;Gheit, Hanane;Joubert, Grgoire;Villard-Truc, Florence;Asselin-Paturel, Carine;Trinchieri, Giorgio;Kaiserlian, Dominique
通讯作者：
Kaiserlian, Dominique
影响因子：
20.3
作者：
Martin-Gayo, Enrique;Sierra-Filardi, Elena;Toribio, Maria L.
通讯作者：
Toribio, Maria L.
影响因子：
32.4
作者：
Hadeiba H;Lahl K;Edalati A;Oderup C;Habtezion A;Pachynski R;Nguyen L;Ghodsi A;Adler S;Butcher EC
通讯作者：
Butcher EC