A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis.
A case for regulatory B cells in controlling the severity of autoimmune-mediated inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis.
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DOI：
10.1016/j.jneuroim.2010.10.037
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发表时间：
2011-01
影响因子：
3.3
通讯作者：
Dittel, Bonnie N.
中科院分区：
文献类型：
--
作者：
Ray, Avijit;Mann, Monica K.;Basu, Sreemanti;Dittel, Bonnie N.
关键词：
多发性硬化（MS）被认为是T细胞介导的自身免疫性疾病，其导致存在与中枢神经系统（CNS）内的单核细胞浸润、脱髓鞘和轴突损伤相关的炎性病变/斑块。迄今为止，FDA批准的MS治疗被认为主要通过调节免疫应答发挥作用。由于自身免疫反应需要免疫系统的多个分支，因此MS治疗剂的直接细胞作用机制尚不明确。MS的小鼠模型，实验性自身免疫性脑脊髓炎（EAE），已在破译MS药物的作用机制。此外，EAE已被广泛用于研究CNS自身免疫中免疫系统的单个组分的贡献。在这方面，已经在由于基因消融和随后用B细胞靶向单克隆抗体（mAb）（抗-CD 20）消除而缺乏B细胞的小鼠中研究了B细胞在EAE中的作用。这两种策略都表明B细胞调节EAE临床疾病的程度，并且在它们不存在的情况下，疾病加重。因此出现了一种新的“调节性B细胞”群体。调节性B细胞功能的一个重复发生的组分是IL-10的产生，IL-10是一种具有强效抗炎特性的多效性细胞因子。B细胞耗竭也表明B细胞，特别是抗体产生，在EAE中起致病作用。使用CD 20 mAb（利妥昔单抗）消除MS中的B细胞已显示出有希望的结果。在这篇综述中，我们将讨论目前的想法B细胞在MS绘图从EAE研究和临床试验中获得的知识，使用靶向B细胞的治疗作用。
Multiple sclerosis (MS) is considered to be a T cell-mediated autoimmune disease that results in the presence of inflammatory lesions/plaques associated with mononuclear cell infiltrates, demyelination and axonal damage within the central nervous system (CNS). To date, FDA approved therapies in MS are thought to largely function by modulation of the immune response. Since autoimmune responses require many arms of the immune system, the direct cellular mechanisms of action of MS therapeutics are not definitively known. The mouse model of MS, experimental autoimmune encephalomyelitis (EAE), has been instrumental in deciphering the mechanism of action of MS drugs. In addition, EAE has been widely used to study the contribution of individual components of the immune system in CNS autoimmunity. In this regard, the role of B cells in EAE has been studied in mice deficient in B cells due to genetic ablation and following depletion with a B cell-targeted monoclonal antibody (mAb) (anti-CD20). Both strategies have indicated that B cells regulate the extent of EAE clinical disease and in their absence disease is exacerbated. Thus a new population of “regulatory B cells” has emerged. One reoccurring component of regulatory B cell function is the production of IL-10, a pleiotropic cytokine with potent anti-inflammatory properties. B cell depletion has also indicated that B cells, in particular antibody production, play a pathogenic role in EAE. B cell depletion in MS using a mAb to CD20 (rituximab) has shown promising results. In this review, we will discuss the current thinking on the role of B cells in MS drawing from knowledge gained in EAE studies and clinical trials using therapeutics that target B cells.
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影响因子：
100.3
作者：
Baxter, Alan G.
通讯作者：
Baxter, Alan G.
影响因子：
20.3
作者：
Carson, Kenneth R.;Evens, Andrew M.;Bennett, Charles L.
通讯作者：
Bennett, Charles L.
DOI：
10.1073/pnas.0402455101
发表时间：
2004-07-27
影响因子：
11.1
作者：
Corcione, A;Casazza, S;Pistoia, V
通讯作者：
Pistoia, V
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：
Dass, Shouvik;Vital, Edward M.;Emery, Paul
通讯作者：
Emery, Paul