T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.
T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.
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NK 细胞中 T-bet 依赖性 S1P5 表达促进淋巴结和骨髓的流出。
DOI：
10.1084/jem.20090525
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发表时间：
2009-10-26
期刊：
影响因子：
--
通讯作者：
Chun J
中科院分区：
文献类型：
--
作者：
Jenne CN;Enders A;Rivera R;Watson SR;Bankovich AJ;Pereira JP;Xu Y;Roots CM;Beilke JN;Banerjee A;Reiner SL;Miller SA;Weinmann AS;Goodnow CC;Lanier LL;Cyster JG;Chun J
在筛选影响血液自然杀伤（NK）细胞的乙基亚硝基脲诱导的小鼠突变期间，我们确定了一种称为Duane的菌株，其中NK细胞在血液和脾脏中减少，但在淋巴结（LN）和骨髓（BM）中增加。淋巴结中NK细胞的积聚反映了其退出淋巴的能力下降。该菌株在Tbx 21（T-bet）内携带点突变，产生缺陷蛋白。Duane NK细胞在鞘氨醇-1-磷酸受体5（S1 P5）转录水平上有30倍的缺陷，S1 P5缺陷小鼠表现出与Duane相似的出口缺陷。染色质免疫沉淀证实了T-bet与S1 pr 5位点的结合。S1 P缺陷小鼠表现出更严重的NK细胞出口阻滞，FTY 720敏感的S1 P1也在NK细胞从LN出口中发挥作用。S1 P5不受CD 69抑制，这是一种可能促进活化NK细胞运输至效应位点的特性。最后，NK细胞在S1 P缺陷小鼠BM内的积累与BM窦状隙中的数量减少相关，表明S1 P在BM排出中的作用。总之，这些发现将S1 P5鉴定为NK细胞从LN和BM流出所需的T-bet诱导的基因。
During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P5) transcript levels, and S1P5-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P1 also plays a role in NK cell egress from LNs. S1P5 is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P5 as a T-bet–induced gene that is required for NK cell egress from LNs and BM.
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影响因子：
5.3
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