B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation.
B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation.
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DOI：
10.1038/srep34594
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发表时间：
2016-10-06
影响因子：
4.6
通讯作者：
Lalive PH
中科院分区：
文献类型：
--
作者：
Bjarnadóttir K;Benkhoucha M;Merkler D;Weber MS;Payne NL;Bernard CCA;Molnarfi N;Lalive PH
实验性自身免疫性脑脊髓炎（EAE）（多发性硬化（MS）的鼠模型）的研究表明，调节性B细胞通过产生抑制性细胞因子来调节疾病的进程。虽然数据表明转化生长因子（TGF）-β1表达在调节B细胞功能中的作用，但该机制尚未在自身免疫性神经炎症中进行测试。在重组小鼠髓鞘少突胶质细胞糖蛋白（rmMOG）诱导的EAE中测试B细胞中TGF-β1表达缺陷的转基因小鼠（B-TGF-β1−/−）。在该模型中，与同窝对照组相比，B-TGF-β1−/−小鼠表现出更早的神经功能缺损发作。B-TGF-β1−/−小鼠EAE易感性加重与CNS辅助性T细胞（Th）1/17应答增强相关。此外，选择性B细胞TGF-β1缺陷增加了髓样树突状细胞（强效专职抗原呈递细胞（APC））的频率和活化，表明B细胞来源的TGF-β1可通过抑制APC活性来抑制Th 1/17应答。总之，我们的数据表明，B细胞可以通过TGF-β1下调APC的功能，进而下调致脑炎性Th 1/17应答，这一发现可能与B细胞靶向治疗相关。
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B–TGF-β1−/−) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B–TGF-β1−/− mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B–TGF-β1−/− mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1–deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies.
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影响因子：
4.4
作者：
Lampropoulou, Vicky;Hoehlig, Kai;Fillatreau, Simon
通讯作者：
Fillatreau, Simon
DOI：
10.1056/nejmoa0706383
发表时间：
2008-02-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hauser, Stephen L;Waubant, Emmanuelle;Smith, Craig H
通讯作者：
Smith, Craig H
影响因子：
11.2
作者：
Bar-Or, Amit;Fawaz, Lama;Smith, Craig H.
通讯作者：
Smith, Craig H.
影响因子：
--
作者：
Benedetti, Luana;Franciotta, Diego;Schenone, Angelo
通讯作者：
Schenone, Angelo
影响因子：
12.8
作者：
Gonnella, PA;Chen, YH;Weiner, HL
通讯作者：
Weiner, HL