Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses.
Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses.
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淋巴细胞昼夜节律的时钟控制淋巴结运输和适应性免疫反应。
DOI：
10.1016/j.immuni.2016.12.011
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发表时间：
2017-01-17
期刊：
影响因子：
32.4
通讯作者：
Scheiermann C
中科院分区：
文献类型：
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作者：
Druzd D;Matveeva O;Ince L;Harrison U;He W;Schmal C;Herzel H;Tsang AH;Kawakami N;Leliavski A;Uhl O;Yao L;Sander LE;Chen CS;Kraus K;de Juan A;Hergenhan SM;Ehlers M;Koletzko B;Haas R;Solbach W;Oster H;Scheiermann C
淋巴细胞在淋巴结（LN）中循环以寻找抗原，这被认为是一个连续的过程。在这里，我们表明，淋巴细胞迁移通过淋巴结和淋巴发生在一个不连续的，昼夜节律的方式。淋巴细胞归巢到淋巴结在夜间发病达到高峰，细胞在白天离开组织。这导致淋巴结和传出淋巴液中淋巴细胞结构的强烈振荡。使用谱系特异性基因消融生物钟功能，我们证明这是依赖于淋巴细胞上的促迁移因子的节律性表达。树突状细胞的数量达到高峰的阶段与淋巴细胞，与昼夜振荡存在于免疫后的疾病严重程度，以诱导实验性自身免疫性脑脊髓炎（EAE）。这些节律被T细胞生物钟的遗传破坏所消除，表明淋巴细胞通过淋巴结迁移的昼夜节律调节，其中免疫的时间对于几周后的适应性免疫应答至关重要。淋巴结和淋巴中的淋巴细胞数量在一天中振荡有节奏的Ccr7和S1pr1表达驱动有节奏的淋巴细胞归巢和外出对免疫和病原体的适应性免疫应答是一天中的时间依赖性的淋巴细胞中生物钟的丢失消除了有节奏的适应性免疫应答淋巴细胞通过淋巴结和淋巴的运输是身体的重要免疫监视机制。Druzd等人（2017）证明这种贩运以昼夜节律的方式发生，并且适应性免疫反应也依赖于一天中的时间，并且当T细胞中的昼夜节律钟功能丧失时被消融。
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later. Lymphocyte numbers in lymph nodes and lymph oscillate over the course of the day Rhythmic Ccr7 and S1pr1 expression drives rhythmic lymphocyte homing and egress Adaptive immune responses to immunization and pathogens are time-of-day dependent Loss of circadian clocks in lymphocytes ablates rhythmic adaptive immune responses Lymphocyte trafficking through lymph nodes and lymph is an important immune surveillance mechanism of the body. Druzd et al. (2017) demonstrate that this trafficking occurs in a circadian manner and that adaptive immune responses are also time-of-day dependent and are ablated when circadian clock function is lost in T cells.