Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE.
Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE.
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百日咳毒素抑制脑源性t细胞浸润并促进Th17-EAE期间b细胞驱动的疾病。
DOI：
10.3390/ijms22062924
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发表时间：
2021-03-13
影响因子：
5.6
通讯作者：
Axtell RC
中科院分区：
文献类型：
--
作者：
Maria Z;Turner E;Agasing A;Kumar G;Axtell RC
百日咳毒素（PTX）是髓鞘抗原免疫诱导的实验性自身免疫性脑脊髓炎（EAE）所必需的辅助佐剂。然而，PTX对髓磷脂特异性T辅助细胞转移诱导的EAE的影响尚不清楚。因此，我们研究了PTX如何影响Th 17转移EAE模型（Th 17-EAE）。我们发现PTX通过抑制Th 17细胞的趋化因子受体依赖性运输而显著降低Th 17-EAE。引人注目的是，PTX还促进了B细胞在CNS中的积累，表明PTX将疾病改变为B细胞依赖性病理。为了确定B细胞的作用，我们比较了PTX对野生型（WT）和B细胞缺陷型（µMT）小鼠中Th 17-EAE的影响。在未接受PTX治疗的情况下，WT和µMT小鼠之间的疾病严重程度相当。相比之下，与WT小鼠相比，使用PTX治疗的µMT小鼠的疾病显著减少，CNS中的致病性Th 17细胞减少。总之，本研究表明，PTX抑制了致病性Th 17细胞的迁移，同时促进了致病性B细胞在Th 17-EAE期间在CNS中的积累。这些数据为过继转移Th 17-EAE提供了有用的方法学信息，此外，描述了另一个重要的实验系统来研究多发性硬化症中B细胞的致病机制。
Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX’s effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.
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影响因子：
15.9
作者：
Haak, Stefan;Croxford, Andrew L.;Waisman, Ari
通讯作者：
Waisman, Ari
影响因子：
3.7
作者：
Iqbal AJ;Regan-Komito D;Christou I;White GE;McNeill E;Kenyon A;Taylor L;Kapellos TS;Fisher EA;Channon KM;Greaves DR
通讯作者：
Greaves DR
炎性小呼林有助于百日咳毒素诱导的IL-1β合成，中性粒细胞血管内爬行和自身免疫性脑脊髓炎。
影响因子：
6.7
作者：
Dumas A;Amiable N;de Rivero Vaccari JP;Chae JJ;Keane RW;Lacroix S;Vallières L
通讯作者：
Vallières L
影响因子：
15.9
作者：
Matsushita, Takashi;Yanaba, Koichi;Tedder, Thomas F.
通讯作者：
Tedder, Thomas F.
DOI：
10.1073/pnas.1008816107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Lu, Changming;Diehl, Sean A.;Teuscher, Cory
通讯作者：
Teuscher, Cory