Tu Lei, Chen Jie, Zhang Hongwei, Duan Lihua
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
Medical College, Xiamen University , Xiamen , China.
Front Immunol. 2017 Mar 3;8:214. doi: 10.3389/fimmu.2017.00214. eCollection 2017.
CD103+ dendritic cells (DCs) have been shown to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBDs) through educating regulatory T (Treg) cells differentiation. However, the mechanism of CD103+ DCs subsets differentiation remains elusive. Interleukin (IL)-4 is a pleiotropic cytokine that is upregulated in certain types of inflammation, including IBDs and especially ulcerative colitis. However, the precise role of IL-4 in the differentiation of CD103+ DCs subpopulation remains unknown. In this study, we observed a repressive role of IL-4 on the CD103+ DCs differentiation in both mouse and human. High-dose IL-4 inhibited the CD103+ DC differentiation. In comparison to CD103- DCs, CD103+ DCs expressed high levels of the co-stimulatory molecules and indoleamine 2,3-dioxygenase (IDO). Interestingly, IL-4 diminished IDO expression on DCs in a dose-dependent manner. Besides, high-dose IL-4-induced bone marrow-derived DCs, and monocyte-derived DCs revealed mature DCs profiles, characterized by increased co-stimulatory molecules and decreased pinocytotic function. Furthermore, DCs generated under low concentrations of IL-4 favored Treg cells differentiation, which depend on IDO produced by CD103+ DCs. Consistently, IL-4 also reduced the frequency of CD103+ DC . Thus, we here demonstrated that the cytokine IL-4 involved in certain types of inflammatory diseases by orchestrating the functional phenotype of CD103+ DCs subsets.
已表明CD103⁺树突状细胞（DCs）通过促进调节性T（Treg）细胞分化在炎症性肠病（IBDs）的发病机制中起关键作用。然而，CD103⁺DCs亚群分化的机制仍不清楚。白细胞介素（IL）-4是一种多效性细胞因子，在某些类型的炎症中上调，包括IBDs，尤其是溃疡性结肠炎。然而，IL-4在CD103⁺DCs亚群分化中的具体作用仍不清楚。在本研究中，我们观察到IL-4在小鼠和人类中对CD103⁺DCs分化均有抑制作用。高剂量IL-4抑制CD103⁺DC分化。与CD103⁻DCs相比，CD103⁺DCs表达高水平的共刺激分子和吲哚胺2,3-双加氧酶（IDO）。有趣的是，IL-4以剂量依赖性方式降低DCs上的IDO表达。此外，高剂量IL-4诱导的骨髓来源DCs和单核细胞来源DCs呈现成熟DCs特征，其特点是共刺激分子增加和胞饮功能降低。此外，在低浓度IL-4条件下产生的DCs有利于Treg细胞分化，这依赖于CD103⁺DCs产生的IDO。一致地，IL-4也降低了CD103⁺DC的频率。因此，我们在此证明细胞因子IL-4通过协调CD103⁺DCs亚群的功能表型参与某些类型的炎症性疾病。
