The role of dendritic cell subsets in 2,4,6-trinitrobenzene sulfonic acid-induced ileitis
The role of dendritic cell subsets in 2,4,6-trinitrobenzene sulfonic acid-induced ileitis
复制标题
DOI：
10.1016/j.jaut.2009.10.002
复制
发表时间：
2010-06-01
影响因子：
12.8
通讯作者：
Ikehara, Susumu
中科院分区：
文献类型：
--
作者：
Hoshino, Shoichi;Inaba, Muneo;Ikehara, Susumu
树突状细胞（DC）广泛分布于淋巴和非淋巴组织中，是获得性免疫的重要启动者，也可通过诱导自我耐受发挥调节作用。然而，DCs是否参与免疫反应的终止尚未得到彻底阐明。在本文中，我们使用 2,4,6-三硝基苯磺酸 (TNBS) 诱导的回肠炎模型（克罗恩病的动物模型）检查了固有层中树突状细胞 (DC) 的动力学运动。从第1天到第3天，增加数量的DC被招募到炎症部位，此时可以清楚地观察到炎症反应，然后随着反应的停止，在第7天逐渐下降到稳态水平。第 3 天观察到 CD11c(+)/B220(-) 常规 DC (cDC) 中的三个 DC 子集：PIR-A/B-high、PIR-A/B-med 和 PIR-A/B- DC：当炎症反应在第 7 天停止时，PIR-A/B-med cDC 的数量增加。共刺激分子（例如 CD86 和 CD54）的表达在PIR-A/B-med DC 与其他两个 cDC 子集或脾 DC 进行比较。此外，PIR-A/B-med cDC的刺激活性低于PIR-A/B-high或PIR-A/B-cDC，并且远低于脾DC。此外，第 7 天，在 PIR-A/B 治疗的 cDC 中明显观察到 IL-10 的信息水平增加，而促炎细胞因子（如 IL-6 和 IL-12）的信息水平较低。这些数据表明，在炎症末期增加的PIR-A/B-med cDCs可能通过向效应T细胞传递无能信号来终止TNBS诱导的回肠炎，这是由于共刺激分子的表达较低和免疫调节细胞因子的产生所致。 (C) 2009 Elsevier Ltd. 保留所有权利。
Dendritic cells (DCs) are widely distributed throughout the lymphoid and nonlymphoid tissues, and are important initiators of acquired immunity and also serve as regulators by inducing self-tolerance. However, it has not been thoroughly clarified whether DCs are involved in the termination of immune responses. In this paper, we have examined the kinetical movement of dendritic cells (DCs) in the lamina propria using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ileitis model (an animal model for Crohn's disease). Increased numbers of DCs were recruited to the inflammatory sites from day 1 to day 3 at which time the inflammatory responses was clearly observed, then gradually decreased to a steady-state level on day 7 along with the cessation of responses. Three subsets of DCs, PIR-A/B-high, PIR-A/B-med, and PIR-A/B- DCs in the CD11c(+)/B220(-) conventional DCs (cDCs) were noted on day 3: the number of PIR-A/B-med cDCs increased when the inflammatory responses ceased on day 7. The expression of costimulatory molecules such as CD86 and CD54 was lower in the PIR-A/B-med DCs compared with the other two cDC subsets or splenic DCs. Furthermore, the stimulatory activity of PIR-A/B-med cDCs was lower than those of PIR-A/B-high or PIR-A/B- cDCs, and far lower than that of splenic DCs. In addition, an increase in the message level of IL-10 was clearly observed in the PIR-A/B-med cDCs on day 7 while that of proinflammatory cytokines such as IL-6 and IL-12 was low. These data demonstrate that PIR-A/B-med cDCs which increase at the final stage of inflammation may be involved in the termination of the TNBS-induced ileitis by the delivery of anergic signals to effector T cells due to the lower expressions of costimulatory molecules and the production of immunoregulatory cytokine. (C) 2009 Elsevier Ltd. All rights reserved.