不同遗传背景对C5aR在银屑病病理中作用的影响  

Effects of different genetic backgrounds on role of C5aR in psoriasis pathogenesis

作　　者：徐砜 郑权友 李桂清 陈戬 许桂莲(指导) XU Feng;ZHENG Quan-You;LI Gui-Qing;CHEN Jian;XU Gui-Lian(Department of Immunology,Basic Medicine College,Army Medical University,Chongqing 400038,China)

机构地区：[1]陆军军医大学基础医学院免疫学教研室,重庆400038 [2]陆军军医大学958医院泌尿外科,重庆400038

出　　处：《中国免疫学杂志》2020年第8期905-909,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金面上项目(81873881)资助。

摘　　要：目的:建立咪喹莫特诱导的银屑病样动物模型,通过比较BALB/c和C57BL/6两种遗传背景的C5aR^+/+和C5aR^-/-小鼠的病理表现及相关指标的变化,探讨不同遗传背景对C5aR在银屑病病理发生中的作用。方法:小鼠分为4组:C5aR^+/+BALB/c、C5aR^-/-BALB/c、C5aR^+/+C57BL/6和C5aR^-/-C57BL/6小鼠组。咪喹莫特涂抹小鼠背部皮肤,诱导银屑病动物模型。依据PASI(psoriasis area severity index)评价各组小鼠的皮损程度;HE染色观察皮损组织的病理学变化;qRT-PCR检测皮损组织中IL-17A mRNA水平;流式细胞术分析引流淋巴结和皮损局部组织中分泌IL-17A的γδT细胞亚群的百分比。结果:与同背景C5aR^+/+小鼠相比,C5aR^-/-小鼠银屑病样表型显著减小;相比BALB/c背景的C5aR^+/+(或C5aR^-/-)小鼠,C57BL/6背景的C5aR^+/+(或C5aR^-/-)小鼠银屑病样皮损和相关指标明显减轻;皮损局部组织和引流淋巴结中分泌IL-17A的γδT细胞亚群百分比显著降低。结论:C5aR在咪喹莫特诱导的银屑病样炎症中发挥重要作用;但遗传背景不同,咪喹莫特诱导的银屑病样小鼠表现也不同:BALB/c遗传背景的C5aR^+/+和C5aR^-/-小鼠比C57BL/6遗传背景的相应C5aR^+/+和C5aR^-/-小鼠更为敏感。Objective:To establish the imiquimod-induced psoriasis animal model,and to investigate the effect of different genetic backgrounds on the role of C5aR in psoriasis pathogenesis by comparing the pathological manifestations and related indicators of C5aR^+/+and C5aR^-/-mice with BALB/c and C57BL/6 genetic backgrounds.Methods:Mice were divided into four groups:C5aR^+/+BALB/c,C5aR^-/-BALB/c,C5aR^+/+C57BL/6 and C5aR^-/-C57BL/6 mice group.Imiquimod was applied to the back skin of mice,and the psoriasis-like animal model was induced to evaluate the skin lesions of each group according to the psoriasis area severity index.Histopathological changes were observed by HE staining.The level of IL-17A mRNA was detected by qRT-PCR.Flow cytometry was performed to analyze the percentage of IL-17A-secreting T cell subpopulation in both the skin lesions and in draining lymphnodes.Results:Compared with C5aR^+/+mice with the same background,the psoriatic phenotype of C5aR^-/-mice was significantly reduced.Compared with BALB/c background C5aR^+/+(or C5aR^-/-)mice,C57BL/6 background C5aR^+/+(or C5aR^-/-)mice showed significantly reduced psoriatic lesions.The percentages of the IL-17A-secreting T cell subpopulation was significantly reduced in both the lesion local tissues and the draining lymph nodes.Conclusion:C5aR plays an important role in imiquimod-induced psoriatic inflammation.However,with different genetic backgrounds,imiquimod-induced psoriatic mice have been showed different manifestations:C5aR^+/+and C5aR^-/-mice with BALB/c genetic backgrounds are more sensitive than C5aR^+/+and C5aR^-/-mice with C57BL/6 genetic backgrounds.

关 键 词：遗传背景 C5AR 银屑病 咪喹莫特 小鼠模型 

分 类 号：R392.2[医药卫生—免疫学]