Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts.
Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts.
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DOI：
10.1126/sciimmunol.aam6202
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发表时间：
2017-06-23
影响因子：
24.8
通讯作者：
Lakkis FG
中科院分区：
文献类型：
--
作者：
Dai H;Friday AJ;Abou-Daya KI;Williams AL;Mortin-Toth S;Nicotra ML;Rothstein DM;Shlomchik WD;Matozaki T;Isenberg JS;Oberbarnscheidt MH;Danska JS;Lakkis FG
尽管缺乏适应性免疫系统，缺乏T、B和NK细胞的小鼠仍能区分自体和异体非自体。当受到同种异体移植物的挑战时，它们会产生一种先天反应，其特征是成熟的单核细胞来源的树突状细胞（dc）的积累，产生IL-12并引发移植物排斥反应。然而，先天免疫系统检测异体非自体产生这些dc的分子机制尚不清楚。为了解决这个问题，我们研究了缺乏T， B， NK细胞的Rag2−/−γc−/−小鼠对同种异体供体移植物的先天反应。我们通过定位克隆发现，编码信号调节蛋白α (SIRPα)基因的供体多态性是受体先天异体识别反应的关键调节因子。在一个或两个Sirpa等位基因上与受体不同的供体引发了先天的同种异体反应。这种反应是由供体SIRPα与受体CD47结合介导的，并受SIRPα-CD47相互作用强度的调节。因此，通过CD47感知SIRPα多态性提供了一种分子机制，通过这种机制，先天免疫系统可以独立于T、B和NK细胞区分自身和异体异体。
Mice devoid of T, B, and NK cells distinguish between self and allogeneic non-self despite the absence of an adaptive immune system. When challenged with an allograft they mount an innate response characterized by accumulation of mature, monocyte-derived dendritic cells (DCs) that produce IL-12 and initiate graft rejection. The molecular mechanisms, however, by which the innate immune system detects allogeneic non-self to generate these DCs are not known. To address this question, we studied the innate response of Rag2−/−γc−/− mice, which lack T, B, NK cells, to grafts from allogeneic donors. We identified by positional cloning that donor polymorphism in the gene encoding signal regulatory protein alpha (SIRPα) is a key modulator of the recipient’s innate allorecognition response. Donors that differed from the recipient in one or both Sirpa alleles elicited an innate alloresponse. The response was mediated by binding of donor SIRPα to recipient CD47 and was modulated by the strength of the SIRPα-CD47 interaction. Therefore, sensing SIRPα polymorphism by CD47 provides a molecular mechanism by which the innate immune system distinguishes between self and allogeneic non-self independently of T, B, and NK cells.
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影响因子：
11.4
作者：
Inagaki, K;Yamao, T;Kasuga, M
通讯作者：
Kasuga, M
影响因子：
17.1
作者：
Chhabra A;Ring AM;Weiskopf K;Schnorr PJ;Gordon S;Le AC;Kwon HS;Ring NG;Volkmer J;Ho PY;Tseng S;Weissman IL;Shizuru JA
通讯作者：
Shizuru JA
DOI：
10.1084/jem.194.4.541
发表时间：
2001-08-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blazar BR;Lindberg FP;Ingulli E;Panoskaltsis-Mortari A;Oldenborg PA;Iizuka K;Yokoyama WM;Taylor PA
通讯作者：
Taylor PA
影响因子：
15.9
作者：
Oberbarnscheidt, Martin H.;Zeng, Qiang;Lakkis, Fadi G.
通讯作者：
Lakkis, Fadi G.
DOI：
10.1073/pnas.0609661104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Ide, Kentaro;Wang, Hui;Ohdan, Hideki
通讯作者：
Ohdan, Hideki