ABCB5 Identifies Immunoregulatory Dermal Cells.
ABCB5 Identifies Immunoregulatory Dermal Cells.
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DOI：
10.1016/j.celrep.2015.08.010
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发表时间：
2015-09-08
期刊：
影响因子：
8.8
通讯作者：
Frank MH
中科院分区：
文献类型：
--
作者：
Schatton T;Yang J;Kleffel S;Uehara M;Barthel SR;Schlapbach C;Zhan Q;Dudeney S;Mueller H;Lee N;de Vries JC;Meier B;Vander Beken S;Kluth MA;Ganss C;Sharpe AH;Waaga-Gasser AM;Sayegh MH;Abdi R;Scharffetter-Kochanek K;Murphy GF;Kupper TS;Frank NY;Frank MH
基于细胞的策略代表了免疫介导疾病治疗的新前沿。然而，缺乏分子定义的免疫调节细胞群的分离标记构成了这一领域的障碍。在这里，我们表明，ATP结合盒成员B5（ABCB 5）识别真皮免疫调节细胞（DIRC）能够发挥治疗免疫调节功能，通过参与程序性细胞死亡1（PD-1）。纯化的Abcb 5 + DIRC抑制T细胞增殖，逃避免疫排斥，归巢到受体免疫组织并在体内诱导TcB。在完全MHC不匹配的同种异体心脏移植模型中，异基因DIRC显著延长了同种异体移植物的存活。阻断DIRC表达的PD-1逆转了DIRC对T细胞活化的抑制作用，抑制了DIRC依赖性Treg诱导，并减弱了DIRC诱导的心脏同种异体移植物存活时间延长，表明DIRC免疫调节功能至少部分通过PD-1介导。我们的研究结果确定ABCB 5 + DIRC作为一个独特的免疫调节细胞群，并建议在细胞免疫治疗中的这种可扩展的细胞亚群的有前途的作用。
Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly-defined immunomodulatory cell populations poses a barrier to this field. Here we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T-cell proliferation, evaded immune rejection, homed to recipient immune tissues and induced Tregs in vivo. In fully MHC-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T-cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.
DOI：
10.1016/j.bbrc.2010.03.040
发表时间：
2010-04-09
影响因子：
3.1
作者：
Izawa, Atsushi;Schatton, Tobias;Frank, Natasha Y.;Ueno, Takuya;Yamaura, Kazuhiro;Pendse, Shona S.;Margaryan, Armen;Grimm, Martin;Gasser, Martin;Waaga-Gasser, Ana Maria;Sayegh, Mohamed H.;Frank, Markus H.
通讯作者：
Frank, Markus H.