CD301b/MGL2+ 单核细胞编排 自身免疫性心脏炎和纤维化
Lee A Meier1,2,3, Jennifer L Auger1,2, Brianna J Engelson1,3
1Center for Immunology (L.A.M., J.L.A., B.J.E., H.M.C., M.I.G.-T., B.A.B.).
Circulation
|February 2, 2018
概括
单核细胞 (MNPs) 通过表达TNF和IL-6等炎症分子驱动自身免疫膜疾病 (MVD). 针对这些途径,包括Syk和VLA-4,为MVD提供了潜在的治疗策略.
科学领域:
- 免疫学
- 心血管生物学
- 病理学
背景情况:
- 膜性心脏病,特别是膜性心脏病 (MVD) 是普遍存在的,但其潜在的细胞和分子机制尚不清楚.
- 自免疫性疾病可能导致严重的纤维炎性MVD,需要对疾病发病和进展途径进行研究.
研究的目的:
- 在T细胞受体转基因小鼠模型中阐明自身免疫性MVD的细胞和分子驱动因素.
- 研究单核细胞 (MNPs) 在MVD病变中的作用.
- 通过将小鼠的发现与人类的风湿性心脏病相关联来确定潜在的治疗点.
主要方法:
- 使用多参数流细胞计和免疫光学来鉴定K/B.g7小鼠中的MV透细胞.
- 在MNP中使用特定MNP群体的基因切除 (CX3CR1+或CD301b/MGL2+MNP) 和条件基因删除 (Syk,VLA-4).
- 对关键的炎症性细胞因子 (TNF,IL-6) 进行了抗体阻塞研究,并使用骨髓模拟小鼠来确定细胞起源和反应.
主要成果:
- 在炎症的MV中表达CX3CR1和CD301b/MGL2的MNP是主要的透细胞,类似于人类风湿性心脏病中发现的细胞.
- 保护小鼠免受MVD发展的CX3CR1+或CD301b/MGL2+MNP的切除.
- 包括Syk,TNF,IL-6,VLA-4和VCAM-1在内的炎症媒介被确定为关键驱动因素,TNF通过TNF受体-1作用于膜细胞.
结论:
- 在该模型中,CD301b/MGL2+MNP对自身免疫性MVD的发病至关重要,并且存在于人类的风湿性心脏病中.
- 关键的炎症分子 (Syk,TNF,IL-6,VLA-4,VCAM-1) 调节了MVD的进展,突出了它们作为治疗点的潜力.
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