Identification of new regulatory B cell subsets suppressing fibrosis

抑制纤维化的新调节性 B 细胞亚群的鉴定

• 批准号: 24659523
• 负责人: FUJIMOTO Manabu
• 金额: $ 2.33万
• 依托单位: University of Tsukuba (2013)Kanazawa University (2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659523/
• 关键词: 線維化; 皮膚免疫; 強皮症; 細胞; 免疫; 皮膚疾患

Recent studies have clarified the protective role of regulatory B cells (Bregs) in various inflammatory and autoimmune diseases. In this study, we studied the role of Bregs in fibortic diseases using sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) model, which is characterized by fibrosis and autoimmune features resembling those of systemic sclerosis (SSc). CD19-deficient (CD19-/-) mice were used as donors or recipients in this model. CD19-/- donors induced more severe Scl-cGVHD than wild-type donors, while CD19-/- recipients showed no significant differences compared with wild-type recipients. IL-10-producing regulatory B cells (B10 cells) were not reconstituted by CD19-/- donor cells, and early adoptive transfer of B10 cells attenuated the augmented manifestations of CD19-/- donor-induced Scl-cGVHD. Therefore, donor-derived B10 cells have a suppressive role in Scl-cGVHD development.

最近的研究阐明了调节性 B 细胞 (Bregs) 在各种炎症和自身免疫性疾病中的保护作用。 在这项研究中，我们使用硬皮病慢性移植物抗宿主病（Scl-cGVHD）模型研究了Bregs在纤维化疾病中的作用，该模型的特点是纤维化和类似于系统性硬化症（SSc）的自身免疫特征。 CD19 缺陷 (CD19-/-) 小鼠被用作该模型中的供体或受体。 CD19-/-供体比野生型供体诱导更严重的Scl-cGVHD，而CD19-/-受体与野生型受体相比没有显着差异。 CD19-/-供体细胞不能重建产生IL-10的调节性B细胞（B10细胞），B10细胞的早期过继转移减弱了CD19-/-供体诱导的Scl-cGVHD的增强表现。因此，供体来源的 B10 细胞在 Scl-cGVHD 发育中具有抑制作用。

项目成果

IL-6 Blockade Attenuates the Development of Murine Sclerodermatous Chronic Graft-Versus-Host Disease

• DOI: 10.1038/jid.2012.226
• 发表时间: 2012-12-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Doanh Le Huu;Matsushita, Takashi;Fujimoto, Manabu
• 通讯作者: Fujimoto, Manabu

Chemokine receptors CCR2 and CX3CR1 regulate skin fibrosis in the mouse model of cytokine-induced systemic sclerosis

• DOI: 10.1016/j.jdermsci.2012.10.010
• 发表时间: 2013-03-01
• 期刊: JOURNAL OF DERMATOLOGICAL SCIENCE
• 影响因子: 4.6
• 作者: Arai, Minako;Ikawa, Yuka;Takehara, Kazuhiko
• 通讯作者: Takehara, Kazuhiko

Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease

• DOI: 10.1182/blood-2012-11-465658
• 发表时间: 2013-04-18
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Doanh Le Huu;Matsushita, Takashi;Fujimoto, Manabu
• 通讯作者: Fujimoto, Manabu