Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran sodium sulfate-induced colitis
Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran sodium sulfate-induced colitis
复制标题
PIR-A/B DCs在右旋糖酐硫酸钠诱导的结肠炎炎症反应中的免疫调节功能
DOI：
10.1007/s00535-013-0879-x
复制
发表时间：
2014
影响因子：
6.3
通讯作者：
Okazaki K
中科院分区：
文献类型：
--
作者：
Kurishima A;Inaba M;Sakaguchi Y;Fukui T;Uchida K;Nishio A;Nomura S;Okazaki K
树突状细胞(DC)在炎症性肠病(IBD)中可能起重要作用，如克罗恩病和溃疡性结肠炎。DC通常被认为是获得性免疫的启动者，也是先天免疫和获得性免疫的调节者。我们采用葡聚糖硫酸钠(DSS)诱导的结肠炎动物模型，观察从结肠中分离的DC在终止DSS诱导的结肠炎中是否具有免疫调节作用。从大肠固有层分离DC，并对其表型、功能和遗传学数据进行分析。结果在稳定状态下，仅检测到PIR-A/Blow传统型DC。DSS治疗后第5天至第7天，PIR-A/BHighcDC出现并逐渐增多，DSS诱导的结肠炎消失。然后进行异基因混合白细胞反应(MLR)。第7天获得的PIR-A/BHighcDCs的刺激活性很低，加入PIR-A/BHighcDCs可抑制MLR中T细胞的增殖，表明PIR-A/BHighcDCs具有免疫调节作用。体内转移实验证实了PIR-A/BHighcDCs的免疫调节作用，表明其对DSS诱导的结肠炎有治疗作用。转化生长因子βI在PIR-A/BHighcDC中的表达水平显著高于PIR-A/BlowcDC，而干扰素-γ在PIR-A/BlowcDC中高度上调，这与PIR-A/BHighcDC对活化的T细胞具有抑制作用的事实相一致。
BackgroundDendritic cells (DCs) may play an important role in forms of inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis. DCs are generally recognized as initiators of acquired immunity and also serve as regulators of both innate and acquired immunity. We used the animal model of colitis induced by dextran sodium sulfate (DSS), and examined whether DCs prepared from the colon show immunoregulatory roles in the termination of DSS-induced colitis.MethodsC57BL/6 mice exposed to DSS for 5 days developed acute colitis. DCs were isolated from the large intestinal lamina propria, and then analyzed for phenotypical, functional, and genetic data.ResultsOnly PIR-A/Blowconventional DCs (cDCs) were detected in the steady state. However, after the treatment of DSS, PIR-A/BhighcDCs appeared and gradually increased from day 5 to day 7, at which time the DSS-induced colitis was terminated. Then, allogeneic mixed leukocyte reaction (MLR) was performed. The stimulatory activity of PIR-A/BhighcDCs obtained on day 7 was very low, and the addition of PIR-A/BhighcDCs suppressed the T cell proliferation in MLR, indicating the immunoregulatory role of PIR-A/BhighcDCs. The immunoregulatory role of PIR-A/BhighcDCs was confirmed by the in vivo transfer experiment, showing their therapeutic effect on DSS-induced colitis. The message level of TGFβi was significantly higher in PIR-A/BhighcDCs, while that of IFN-γ was highly upregulated in PIR-A/BlowcDCs, being well in accordance with the fact that PIR-A/BhighcDCs showed a suppressive function against activated T cells.ConclusionPIR-A/BhighcDCs showed a suppressive function against activated T cells by producing inhibitory cytokines.