High mobility group box 1 protein suppresses T cell-mediated immunity via CD11clowCD45RBhigh dendritic cell differentiation
High mobility group box 1 protein suppresses T cell-mediated immunity via CD11clowCD45RBhigh dendritic cell differentiation
复制标题
高迁移率族盒 1 蛋白通过 CD11c（低）CD45RB（高）树突状细胞分化抑制 T 细胞介导的免疫。
DOI：
10.1016/j.cyto.2011.01.008
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发表时间：
2011-05-01
期刊：
影响因子：
3.8
通讯作者：
Sheng, Zhi-yong
中科院分区：
文献类型：
--
作者：
Liu, Qing-yang;Yao, Yong-ming;Sheng, Zhi-yong
目的：高迁移率族蛋白B1（HMGB 1）是一种晚期促炎细胞因子，在免疫调节中起重要作用。然而，HMGB 1是否能够诱导树突状细胞（DC）亚群的活化和分化，进而调节T细胞的免疫功能尚不清楚。本研究通过体外培养雄性BALB/c小鼠脾脏DC，观察HMGB 1对脾脏DC分化的影响，以及HMGB 1对DC亚群CD 11 c（low）、CD 45 RB（high）和CD 11 c（high）、CD 45 B（low）的影响。CD 11 c（高）CD 45 RB（低）DC和CD 4（+）T细胞。与其对应物（CD 11 c（高）CD 45 RB（低）DC）相比，用HMGB 1处理后，CD 11 c（低）CD 45 RB（高）DC的百分比显著增加。结果发现，与HMGB 1诱导的CD 11 c（high）CD 45 RB（low）DCs分泌IL-12逐渐增加不同，HMGB 1诱导的CD 11 c（low）CD 45 RB（high）DCs分泌IL-10与HMGB 1刺激之间呈现明显的剂量依赖性反应。为了验证CD 4 + T细胞的变化是否主要与HMGB 1介导的脾DCs向CD 11 c（低）CD 45 RB（高）DCs的分化有关，用抗IL-12受体（IL-12 R）或抗IL-10 R单克隆抗体抑制CD 11 c（高）CD 45 RB（低）DC或CD 11 c（低）CD 45 RB（高）DC在CD 4（+）T细胞混合淋巴细胞反应培养。在CD 4（+）T细胞+CD 11 c（high）CD 45 RB（low）DCs或CD 11 c（low）CD 45 RB（high）DCs混合淋巴细胞反应中，经抗IL-12 R或抗IL-10 R单克隆抗体处理后，这些DCs对T细胞的诱导作用明显受到抑制。这些数据表明，HMGB 1可以诱导脾DCs分化为CD 11 c（低）CD 45 RB（高）体外培养DC后Th 1向Th 2转化，T淋巴细胞免疫功能增强。此外，HMGB 1对T细胞向Th 2分化的作用与抑制CD 11 c（高）CD 45 RB（低）DC中IL-12的产生无关。(C)2011爱思唯尔有限公司保留所有权利。
Aim: High mobility group box 1 protein (HMGB1) has been identified as a late proinflammatory cytokine and plays a key role in immune regulation. However, it is not yet clear whether HMGB1 can induce the activation and differentiation of dendritic cell (DC) subsets and subsequently modulate immune function of T cells. This study was performed to investigate the effect of HMGB1 on the differentiation of splenic DCs and its influence on T cell-mediated immunity in terms of DC subsets CD11c(low)CD45RB(high) DCs and CD11c(high)CD45B(low) DCs in male BALB/c mice spleens in vitro.Results: MACS microbeads were used to isolate splenic DCs, CD11c(low)CD4SRB(high) DCs. CD11c(high)CD45RB(low) DCs and CD4(+) T cells. The percentage of CD11c(low)CD45RB(high) DCs was significantly increased after treatment with HMGB1 compared to their counterparts (CD11c(high)CD45RB(low) DCs). It was found that unlike the gradually increasing interleukin (IL)-12 secretion of CD11c(high)CD45RB(low) DCs induced by HMGB1, CD11c(low)CD45RB(high) DCs showed a obvious dose-dependent response between IL-10 production and HMGB1 stimulation. In order to verify whether the alteration of CD4(+) T cells was mainly associated with the differentiation of splenic DCs mediated by HMGB1 to CD11c(low)CD45RB(high) DCs, anti-IL-12 receptor (IL-12R) or anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs in CD4(+) T cells mixed lymphocyte reaction culture. After treatment with anti-IL-12R or anti-IL-10R monoclonal antibody in CD4(+) T cells + CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs mixed lymphocyte reaction, the induction of these DCs on T cells was inhibited dramatically.Conclusion: These data demonstrated that HMGB1 might induce the differentiation of splenic DCs to CD11c(low)CD45RB(high) DCs followed by shifting of Th1 to Th2 with enhancement of T lymphocyte immune function in vitro. Also, the effect of HMGB1 on T cell differentiation to Th2 was not associated with the inhibition of IL-12 production in CD11c(high)CD45RB(low) DCs. (C) 2011 Elsevier Ltd. All rights reserved.