NB-UVB对表皮树突状细胞介导的特应性皮炎Th2免疫反应的调控作用及分子机制研究

Atopic dermatitis (AD) is chronic, relapsing, highly pruritic inflammatory skin disease which may have the significant adverse effects on patient's quality of life. AD is characterized by inflammatory processes in which the T helper type2 (Th2) cells are crucial for the initiation and maintenance of allergic immune responses. Recently, it has been clarified an integral role of dendritic cells (DCs) in the cellular cascade that initiate Th2 responses in AD. DCs are without a doubt important key skin cells that connect information from the environment with the innate and adaptive immune system. TSLP receptors are able to active DCs and induce inflammatory Th2 cell response in response to antigen. Many studies have showed the therapy effect of NB-UVB in AD, however, the mechanism has not yet been studied in AD. We suggest that NB-UVB may have immunoregulative effect on Th2 immune response of AD via DCs. This project aims to evaluate the therapeutic effects and to clarify the molecular mechanism of NB-UVB on skin lesions of AD patients and mite allergen-induced AD mouse model. We will observe the skin (skin manifestation, histology, infiltrated cells etc.), serum (IgE, cytockines expression etc.)and the interactions between NB-UVB and DCs, which will help clarify the mechanism of NB-UVB in AD, and develop new insight on therapy or prevention.

特应性皮炎（AD）是一种慢性、复发性、瘙痒性皮肤病，严重影响患者生活质量。表皮树突状细胞（DCs）包括朗格汉斯细胞（LCs) 和炎症性树突状表皮细胞（IDECs)，在特应性皮炎Th2免疫炎症的启动、发展和维持中起着重要作用。研究已证实LCs和IDECs表面TSLP受体激活可促进其成熟并进一步发挥抗原提呈和诱导Th2细胞分化的作用，从而参与AD免疫炎症过程。NB-UVB治疗AD疗效确切但分子机制尚未明确，推测可能通过影响表皮树突状细胞的活化和功能发挥免疫调节和治疗作用。为验证这一假说，本课题将在AD患者和抗原诱导的AD动物模型两个层面研究不同治疗方案的NB-UVB对表皮树突状细胞活化、抗原提呈及诱导Th2细胞分化作用的影响，并重点关注NB-UVB对“表皮DCs-TSLPR-Th2”途径活化的影响，以初步阐明NB-UVB治疗AD的分子免疫机制，为更好的制定AD光疗方案奠定理论基础。

特应性皮炎（AD）是一种慢性、复发性、瘙痒性皮肤病，严重影响患者生活质量。探讨窄谱中波紫外线（NB-UVB）治疗特应性皮炎（atopic dermatitis, AD）可能的免疫学机制。 在DC2.4细胞系中以TSLP刺激诱导树突状细胞（dendritic cells, DCs）活化继而用NB-UVB照射，观察Th2细胞因子的表达情况，并采用T/B缺陷的Rag1-/-小鼠制备MC903诱导的AD小鼠模型进行验证。 在体外DCs培养中，TSLP可促进DCs细胞活化并上调Th2细胞因子表达，经NB-UVB照射后，DCs活化程度降低，Th2细胞因子IL-4（t=6.955, P=0.0011）和IL-13（t=2.875, P=0.0282）相对表达量下降。在AD小鼠模型中，NB-UVB照射可减轻MC903诱导的AD样皮炎，并且Th2细胞因子IL-4（t=8.964, P<0.0001）及IL-13（t=4.073, P=0.0036）mRNA相对表达量均显著下调，差异具有统计学意义。在DCs（F=92.13, P<0.0001）及小鼠（t=4.122, P=0.0017）中，NB-UVB照射所致的免疫抑制作用均伴随着TSLP受体TSLPR表达水平下调，差异均有统计学意义。 体外实验和动物研究结果提示NB-UVB可通过下调TSLPR、抑制DCs细胞活化从而抑制Th2炎症反应是其治疗AD的可能机制之一。