Peripheral elimination of the sympathetic nervous system stimulates immunocyte retention in lymph nodes and ameliorates collagen type II arthritis

Peripheral elimination of the sympathetic nervous system stimulates immunocyte retention in lymph nodes and ameliorates collagen type II arthritis
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DOI:
10.1016/j.bbi.2016.02.006
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发表时间:
2016-05-01
影响因子:
15.1
通讯作者:
Straub, Rainer H.
Straub, Rainer H.
中科院分区:
医学1区
文献类型:
--
作者:
Klatt, Susanne;Stangl, Hubert;Straub, Rainer H.

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目的:在H型胶原诱导的关节炎(CIA)中,交感神经系统(SNS)的早期激活是促炎性的。在这里,我们想找到新的靶器官有助于促炎SNS的影响。此外,我们想澄清的重要性,SNS调制的免疫细胞migration.Methods:一种新的技术,称为空间能量消耗配置(SEEC)的开发,以证明身体领域的高能量需求(寻找新的目标)。我们研究了归巢标记的细胞在体内,淋巴细胞表达的CCR 7,上清液浓度的CCL 21,和血清水平的鞘氨醇-1-磷酸(S1 P)在交感神经切除控制/arthriticanimals.Results:在关节炎的过程中,SEEC确定了一个早期显着增加的能量消耗在引流淋巴结和脾脏(无处!)。虽然早期交感神经切除术改善了后来的疾病,早期交感神经切除术增加的能量消耗,器官重量,和细胞数量在关节炎的次级淋巴器官,可能是淋巴细胞滞留的迹象(也在对照组)。SNS的消除保留了淋巴结细胞,淋巴结细胞上CCR 7的表达升高,并且增加了CCL 21。血清中的SIP水平,一个重要的因素淋巴细胞的出口,关节炎比对照组动物更高。交感神经切除术将关节炎动物的SIP水平降低至对照水平。保留的免疫细胞从引流淋巴结的交感神经切除捐赠者交感神经切除受体转移显着增加关节炎的严重程度超过weeks.Conclusions:通过使用SEEC技术,我们确定引流淋巴结和脾脏作为SNS的主要靶器官。数据显示SNS增加淋巴细胞从引流淋巴结的流出以刺激关节炎炎症。(C)2016 Elsevier Inc. All rights reserved.
Objectives: In collagen type H-induced arthritis (CIA), early activation of the sympathetic nervous system (SNS) is proinflammatory. Here, we wanted to find new target organs contributing to proinflammatory SNS effects. In addition, we wanted to clarify the importance of SNS-modulated immunocyte migration.Methods: A new technique termed spatial energy expenditure configuration (SEEC) was developed to demonstrate bodily areas of high energy demand (to find new targets). We studied homing of labeled cells in vivo, lymphocyte expression of CCR7, supernatant concentration of CCL21, and serum levels of sphingosine-1-phosphate (S1P) in sympathectomized control/arthritic animals.Results: During the course of arthritis, SEEC identified an early marked increase of energy expenditure in draining lymph nodes and spleen (nowhere else!). Although early sympathectomy ameliorated later disease, early sympathectomy increased energy consumption, organ weight, and cell numbers in arthritic secondary lymphoid organs, possibly a sign of lymphocyte retention (also in controls). Elimination of the SNS retained lymph node cells, elevated expression of CCR7 on lymph node cells, and increased CCL21. Serum levels of SIP, an important factor for lymphocyte egress, were higher in arthritic than control animals. Sympathectomy decreased SIP levels in arthritic animals to control levels. Transfer of retained immune cells from draining lymph nodes of sympathectomized donors to sympathectomized recipients markedly increased arthritis severity over weeks.Conclusions: By using the SEEC technique, we identified draining lymph nodes and spleen as major target organs of the SNS. The data show that the SNS increases egress of lymphocytes from draining lymph nodes to stimulate arthritic inflammation. (C) 2016 Elsevier Inc. All rights reserved.