Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses.
Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses.
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DOI：
10.4049/jimmunol.1302079
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发表时间：
2013-11-15
期刊：
影响因子：
--
通讯作者：
Porgador A
中科院分区：
文献类型：
--
作者：
Brusilovsky M;Cordoba M;Rosental B;Hershkovitz O;Andrake MD;Pecherskaya A;Einarson MB;Zhou Y;Braiman A;Campbell KS;Porgador A
KIR 2DL 4（CD 158 d）是人NK细胞中杀伤细胞Ig样受体（KIR）家族的独特成员，其可诱导静息NK细胞中的细胞因子产生和细胞溶解活性。据报道，通常仅由胎儿来源的滋养层细胞表达的可溶性HLA-G是KIR 2DL 4的配体;然而，KIR 2DL 4表达不限于胎盘，并且可以在外周血NK细胞的CD 56 high亚群中发现。我们证明了KIR 2DL 4可以与上皮或成纤维细胞来源的细胞表达的替代配体相互作用。全基因组高通量siRNA筛选显示，KIR 2DL 4对细胞表面配体的识别直接受硫酸乙酰肝素（HS）葡糖胺3-O-磺基转移酶3B 1（HS 3ST 3B 1）调节。发现KIR 2DL 4与HS/肝素直接相互作用，并且KIR 2DL 4的D 0结构域对于这种相互作用是必需的。因此，外源性HS/肝素可以调节表达KIR 2DL 4的NK细胞和HEK 293 T细胞（HEK 293 T-2DL 4）的细胞因子产生，并诱导KIR 2DL 4差异定位于rab 5+和rab 7+内体，从而导致细胞因子产生的下调和受体的降解。此外，我们发现多配体蛋白聚糖-4（SDC 4）HS蛋白聚糖（HSPG）和KIR 2DL 4的密切相互作用直接影响受体内吞作用和膜运输。
KIR2DL4 (CD158d) is a distinct member of the killer cell Ig-like receptor (KIR) family in human NK cells that can induce cytokine production and cytolytic activity in resting NK cells. Soluble HLA-G, normally expressed only by fetal-derived trophoblast cells, was reported to be a ligand for KIR2DL4; however, KIR2DL4 expression is not restricted to the placenta and can be found in CD56high subset of peripheral blood NK cells. We demonstrated that KIR2DL4 can interact with alternative ligand(s), expressed by cells of epithelial or fibroblast origin. A genome-wide high-throughput siRNA screen revealed that KIR2DL4 recognition of cells surface ligand(s) is directly regulated by heparan sulfate (HS) glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1). KIR2DL4 was found to directly interact with HS/heparin, and the D0-domain of KIR2DL4 was essential for this interaction. Accordingly, exogenous HS/heparin can regulate cytokine production by KIR2DL4-expressing NK cells and HEK293T cells (HEK293T-2DL4) and induces differential localization of KIR2DL4 to rab5+ and rab7+ endosomes, thus leading to down-regulation of cytokine production and degradation of the receptor. Furthermore, we showed that intimate interaction of syndecan-4 (SDC4) HS Proteo-Glycan (HSPG) and KIR2DL4 directly affects receptor endocytosis and membrane trafficking.
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影响因子：
2.9
作者：
Krivov, Georgii G.;Shapovalov, Maxim V.;Dunbrack, Roland L., Jr.
通讯作者：
Dunbrack, Roland L., Jr.
DOI：
10.1073/pnas.91.23.11035
发表时间：
1994-11-08
影响因子：
11.1
作者：
GALLO, RL;ONO, M;BERNFIELD, M
通讯作者：
BERNFIELD, M
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
2
作者：
Ito, Kenichiro;Higai, Koji;Matsumoto, Kojiro
通讯作者：
Matsumoto, Kojiro
DOI：
10.1590/s0001-37652009000300007
发表时间：
2009-09-01
期刊：
Anais da Academia Brasileira de Ciências
影响因子：
--
作者：
Dreyfuss, Juliana L.;Regatieri, Caio V.;Nader, Helena B.
通讯作者：
Nader, Helena B.