Therapeutic Approach for Allergic or Autoimmune Diseases by Modulation of CD25+CD4+ T Cells

虽然紫外线B （UVB）诱导树突状细胞（DCs），如朗格汉斯细胞（LCs）的凋亡和功能紊乱，但它也刺激一些树突状细胞在体内照射后成熟。为了分析其对dc的相互作用，我们用人单核细胞来源的dc （MoDCs）体外阐明了UVB对dc的直接作用。50 ~ 200 J/m^2的UVB刺激了MoDCs的成熟，1)增强了CD86和HLA-DR等共刺激分子的表达，2)在mRNA和蛋白质水平上增强了IL-1β、IL-6、IL-8、IL-10和TNF-α的产生，3)增强了每个细胞的异源刺激能力，而超过剂量则诱导凋亡细胞死亡。UVB后对MoDCs的Western-blot分析显示p38和c-JUN n-末端激酶(JNK)-丝裂原活化蛋白激酶（MAPKs）的磷酸化呈剂量依赖性，但细胞外信号调节激酶（ERK）的磷酸化不存在剂量依赖性。P38 mapk抑制剂SB203580对uvb诱导的MoDCs成熟和凋亡均有抑制作用。有趣的是，经历凋亡的MoDCs表现出HLA-DR的表达增强，而CD86抗原的表达上调，这表明它们具有耐受性表型。因此，我们的研究揭示了UVB的双重作用，根据剂量的不同，UVB主要通过p38 mapk途径刺激MoDCs成熟或诱导细胞凋亡。

Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DCs), e.g. Langerhans cells (LCs), it also stimulates some LCs into maturation after irradiation in vivo. To analyze its reciprocal effects on DCs, we elucidated the direct effect of UVB on DCs in vitro using human monocyte-derived DCs (MoDCs). UVB from 50 to 200 J/m^2 stimulated the maturation of MoDCs with 1) augmented expression of co-stimulatory molecules such as CD86 and HLA-DR, 2) enhanced production of IL-1β, IL-6, IL-8, IL-10 and TNF-α at both the mRNA and protein levels, and 3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDCs after UVB demonstrated a dose-dependent phosphorylation of p38-and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPKs), but not that of extracellular signal-regulated kinases (ERK). P38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDCs. Interestingly, MoDCs that had undergone apoptosis exhibited an augmented expression of HLA-DR without up-regulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDCs, depending on the dosage, mainly via the p38 MAPK-pathway.