调节性B细胞之B细胞连接蛋白在特应性皮炎小鼠模型中的作用

Atopic dermatitis (AD) is considered to result from a dysregulation of the normal.interactions between the environment and genes, defects in skin barrier function,.and systemic and local immunological responses. The contribution of the immune.response to the pathogenesis of AD has been attributed to dendritic cell sinaling,.T-helper cell dysregulation, eosinophil accumulation and so on. Besides the.production of antibody from the classical B cells, the issue whether regulatory B.cells (Bregs) are involved in the regulation of inflammation associated with AD is.yet unsolved. Bregs play a role in the pathogesis of some diseases including.allergic contact dermatitis and asthma through suppressing excessive.inflammation via the production of IL-10 and TGF-β. To investigate the role of.Bregs in AD mice model, ovalbumin-sensitized allergic skin inflammation was.assessed in BLNK(-/-) mice (B-cell linker protein, BLNK, an essential component of.B cell antigen receptor signaling) and IL-10(-/-) mice. The morphology of.epidermis and dermis will be observed. The number of CD4(+) T cells, CD8(+) T.cells and CD19(+) B cells will be analyzed in the lesion via immunohistochemistry..The level of IL-10, IL-4, IL-5, IL-13, IFN-γ and IL-17A in the lesion will be.measured via real time RT-PCR. The frequency and number of CD4(+) T cells, CD8(+).T cells, CD19(+)CD5(+)B10 cells and CD4(+)CD25(+)Foxp3(+) T cells in the.peripheral blood, spleen and draining lymph node will be determined. The above.parameters will be measured after adoptive transfer of splenic CD1dhiCD5(+) B.cells from wild-type mice to BLNK(-/-) mice and IL-10(-/-) mice.The research may.provide us new perspectives in the pathophysiology of AD and may have implications.for B-cell-targeted therapies for the treatment of AD.

特应性皮炎（atopic dermatitis，AD）发病机制复杂，涉及多种免疫细胞。B细.胞除产生抗体外，在AD发病过程中是否存在调节作用少有研究。已知B细胞可通过分.泌IL-10抑制变应性接触性皮炎和参与小鼠哮喘模型的调节，因此我们假设其通过同一机制参.与AD的发病过程。我们以野生型C57BL/6小鼠为对照组，以IL-10(-/-)小鼠和BLNK(-/-)小鼠（.B-cell linker protein， B细胞连接蛋白，是B细胞抗原受体信号途径的基本成分）为实验组.，通过外用卵清蛋白诱发AD小鼠模型的方法，检测对比小鼠皮损、外周血、引流淋巴结和脾脏.的炎症细胞及炎症因子的变化，再将对照小鼠脾脏来源的CD1dhiCD5+调节性B细胞分离纯化回.输入实验小鼠模型，检测上述指标的变化，从而探索调节性B细胞通过BLNK对AD的调节作用。