The role of IL-10 and TGF-beta1 secretion by B lymphocytes in lupus prone mice

B淋巴细胞分泌IL-10和TGF-β1在狼疮易感小鼠中的作用

• 批准号: 108052102
• 负责人: Dr. Lino Lars Teichmann
• 金额: --
• 依托单位: Department of Immunology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/108052102?language=en
• 关键词: role; IL; 10; TGF; beta1

B cells (B lymphocytes) play a major role in the pathogenesis of systemic lupus erythematosus and other autoimmune disorders. Efforts to understand the mechanisms by which B cells participate in the development and maintenance of autoimmune diseases have been boosted by the clinical success of B cell modulatory therapies. Recent studies indicate that similar to the situation with T cells not only pathogenic but also regulatory B cells (Bregs) are contained in the B cell compartment. The existence of Bregs could be demonstrated in murine models of rheumatoid arthritis, multiple sclerosis, diabetes mellitus type 1, inflammatory bowel disease and systemic lupus erythematosus. There is evidence that Bregs are particularly generated during B cell reconstitution after anti-CD20 mediated B cell depletion. The regulatory capacity of B cells has been ascribed to the secretion of the cytokines Interleukin 10 (IL-10) and Transforming growth factor β1 (TGF-β1). It stands to reason that activated B cells could be regulating T cells and themselves at the same time by the release of IL-10 and TGF-β1. We plan to test this hypothesis in a murine model of systemic lupus erythematosus (MRL/lpr) by B cell specific deletion of IL-10 or TGF-β1. Moreover, we will investigate whether Bregs can be induced by anti-CD20 mediated B cell depletion in MRL/lpr mice to establish Breg induction as a general mechanism of CD20 targeted therapy. We will conduct further experiments to shed light on the context in which Bregs secrete anti-inflammatory cytokines.

B细胞（B淋巴细胞）在系统性红斑狼疮和其他自身免疫性疾病的发病机制中起主要作用。B细胞调节疗法的临床成功促进了对B细胞参与自身免疫性疾病发展和维持机制的理解。最近的研究表明，与T细胞的情况类似，B细胞室中不仅含有致病性B细胞，也含有调节性B细胞（Bregs）。在类风湿关节炎、多发性硬化症、1型糖尿病、炎症性肠病和系统性红斑狼疮的小鼠模型中可以证实Bregs的存在。有证据表明，在抗cd20介导的B细胞耗竭后的B细胞重构过程中，Bregs特别产生。B细胞的调节能力归因于细胞因子白介素10 （IL-10）和转化生长因子β1 （TGF-β1）的分泌。按理说，活化的B细胞可能同时通过释放IL-10和TGF-β1来调节T细胞和自身。我们计划在系统性红斑狼疮（MRL/lpr）小鼠模型中通过B细胞特异性缺失IL-10或TGF-β1来验证这一假设。此外，我们将研究抗CD20介导的B细胞耗尽是否可以在MRL/lpr小鼠中诱导Breg，以建立Breg诱导作为CD20靶向治疗的一般机制。我们将进行进一步的实验，以阐明Bregs分泌抗炎细胞因子的背景。