高迁移率族蛋白 B1 可通过 CD11c(low)CD45RB(high) 树突状细胞分化抑制 T 细胞介导的免疫。
High mobility group box 1 protein suppresses T cell-mediated immunity via CD11c(low)CD45RB(high) dendritic cell differentiation.
机构信息
Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, PR China.
出版信息
Cytokine. 2011 May;54(2):205-11. doi: 10.1016/j.cyto.2011.01.008. Epub 2011 Feb 5.
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)CD45RB(low) DCs in male BALB/c mice spleens in vitro.
RESULTS
MACS microbeads were used to isolate splenic DCs, CD11c(low)CD45RB(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-10 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.
目的
高迁移率族蛋白 B1（HMGB1）已被鉴定为晚期促炎细胞因子，在免疫调节中发挥关键作用。然而，目前尚不清楚 HMGB1 是否能诱导树突状细胞（DC）亚群的激活和分化，进而调节 T 细胞的免疫功能。本研究旨在探讨 HMGB1 对雄性 BALB/c 小鼠脾脏中 DC 亚群 CD11c（低）CD45RB（高）DC 和 CD11c（高）CD45RB（低）DC 体外分化的影响及其对 T 细胞介导的免疫功能的影响。
结果
使用 MACS 微珠分离脾 DC、CD11c（低）CD45RB（高）DC、CD11c（高）CD45RB（低）DC 和 CD4（+）T 细胞。与对照组（CD11c（高）CD45RB（低）DC）相比，用 HMGB1 处理后 CD11c（低）CD45RB（高）DC 的比例明显增加。结果发现，与 HMGB1 诱导的 CD11c（高）CD45RB（低）DC 中 IL-12 分泌逐渐增加不同，CD11c（低）CD45RB（高）DC 表现出与 HMGB1 刺激之间呈明显的剂量依赖性 IL-10 产生反应。为了验证 CD4（+）T 细胞的改变是否主要与 HMGB1 介导的脾 DC 向 CD11c（低）CD45RB（高）DC 的分化有关，用抗 IL-12 受体（IL-12R）或抗 IL-10R 单克隆抗体抑制 CD4（+）T 细胞混合淋巴细胞反应培养中 CD11c（高）CD45RB（低）DC 或 CD11c（低）CD45RB（高）DC 的作用。在用抗 IL-12R 或抗 IL-10 单克隆抗体处理 CD4（+）T 细胞+CD11c（高）CD45RB（低）DC 或 CD11c（低）CD45RB（高）DC 混合淋巴细胞反应后，这些 DC 对 T 细胞的诱导作用明显受到抑制。
结论
这些数据表明，HMGB1 可能诱导脾 DC 向 CD11c（低）CD45RB（高）DC 的分化，随后通过增强 T 淋巴细胞免疫功能向 Th2 转移，从而导致体外 Th1 向 Th2 的转移。此外，HMGB1 对 T 细胞向 Th2 分化的影响与抑制 CD11c（高）CD45RB（低）DC 中 IL-12 的产生无关。
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