Combinatorial guidance by CCR7 ligands for T lymphocytes migration in co-existing chemokine fields.
Combinatorial guidance by CCR7 ligands for T lymphocytes migration in co-existing chemokine fields.
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DOI：
10.1371/journal.pone.0018183
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发表时间：
2011-03-25
期刊：
影响因子：
3.7
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Nandagopal S;Wu D;Lin F
趋化因子介导淋巴细胞在淋巴组织中的运输和定位，这对于免疫监视和免疫应答至关重要。特别是，CCR7配体CCL21在将T细胞募集到次级淋巴组织（secondary lymphoid tissue，简称NHL）中起重要作用。此外，CCL21与另一种CCR7配体CCL19一起指导T细胞在细胞内的导航和区室化。然而，这两种趋化因子调节细胞运输和定位的不同作用尚不清楚。在这项研究中，我们探讨了共存的CCL19和CCL21浓度场对引导T细胞迁移的影响。使用微流控装置，可以配置单一和叠加的趋化因子领域，我们表明，在生理梯度条件下，人外周血T细胞趋化CCL21，但不是CCL19。此外，T细胞在CCL21的均匀背景中从CCL19梯度迁移。这种排斥性迁移反应是通过基于CCL19和CCL21对CCR7信号传导的竞争以及两种趋化因子对CCR7脱敏的差异能力的数学建模来预测的。这些结果表明CCL19和CCL21对表达CCR7的白细胞的迁移和运输的新的组合引导机制。
Chemokines mediate the trafficking and positioning of lymphocytes in lymphoid tissues that is crucial for immune surveillance and immune responses. In particular, a CCR7 ligand, CCL21, plays important roles in recruiting T cells to secondary lymphoid tissues (SLT). Furthermore, CCL21 together with another CCR7 ligand, CCL19, direct the navigation and compartmentation of T cells within SLT. However, the distinct roles of these two chemokines for regulating cell trafficking and positioning are not clear. In this study, we explore the effect of co-existing CCL19 and CCL21 concentration fields on guiding T cell migration. Using microfluidic devices that can configure single and superimposed chemokine fields we show that under physiological gradient conditions, human peripheral blood T cells chemotax to CCL21 but not CCL19. Furthermore, T cells migrate away from the CCL19 gradient in a uniform background of CCL21. This repulsive migratory response is predicted by mathematical modeling based on the competition of CCL19 and CCL21 for CCR7 signaling and the differential ability of the two chemokines for desensitizing CCR7. These results suggest a new combinatorial guiding mechanism by CCL19 and CCL21 for the migration and trafficking of CCR7 expressing leukocytes.
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影响因子：
2.2
作者：
LAUFFENBURGER, DA;ZIGMOND, SH
通讯作者：
ZIGMOND, SH
DOI：
10.1073/pnas.97.23.12694
发表时间：
2000-11-07
影响因子：
11.1
作者：
Luther, SA;Tang, HL;Cyster, JG
通讯作者：
Cyster, JG
影响因子：
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作者：
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通讯作者：
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影响因子：
6.1
作者：
Lin, Francis;Butcher, Eugene C.
通讯作者：
Butcher, Eugene C.
影响因子：
3.7
作者：
Knapp, DM;Helou, EF;Tranquillo, RT
通讯作者：
Tranquillo, RT