Antigen-Specific TGF-β-Induced Regulatory T Cells Secrete Chemokines, Regulate T Cell Trafficking, and Suppress Ongoing Autoimmunity
Antigen-Specific TGF-β-Induced Regulatory T Cells Secrete Chemokines, Regulate T Cell Trafficking, and Suppress Ongoing Autoimmunity
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DOI：
10.4049/jimmunol.1004112
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发表时间：
2011-08-15
影响因子：
4.4
通讯作者：
DiPaolo, Richard J.
中科院分区：
文献类型：
--
作者：
Nguyen, Thanh-Long M.;Sullivan, Nicole L.;DiPaolo, Richard J.
使用调节性T细胞（Tregs）调节持续炎症的能力正在深入研究中。目前正在开发诱导和扩增ag特异性treg的策略，需要确定各种类型的treg是否在与持续疾病相关的炎症条件下具有抑制作用。在这项研究中，我们报道了tgf - β诱导的Tregs （iTregs）和自身免疫性胃炎中主要自我抗原特异性扩增的Tregs，当在正在进行的疾病过程的后期给予时，可以抑制炎症和相关病理。转移的iTregs定位于胃，维持Foxp3和抑制功能，并参与几种不同的机制来缓解疾病进展。除了抑制胃中炎症细胞因子的产生和防止壁细胞的破坏外，我们还发现iTreg分泌大量趋化因子并调节iTreg和效应T细胞运输到胃中。这些数据支持了利用itreg治疗自身免疫和炎症性疾病的努力，并为itreg介导的免疫抑制的生物学机制提供了新的见解。免疫学杂志，2011,18(7):1745-1753。
The ability to regulate ongoing inflammation using regulatory T cells (Tregs) is under intense investigation. Strategies to induce and expand Ag-specific Tregs are being developed, and whether various types of Tregs are suppressive in the inflammatory conditions associated with ongoing disease needs to be determined. In this study, we report that TGF-beta-induced Tregs (iTregs) and expanded Tregs specific for a major self-Ag in autoimmune gastritis suppress inflammation and associated pathology when administered late in the process of ongoing disease. Transferred iTregs localized to the stomach, maintained Foxp3 and suppressor functions, and engaged several distinct mechanisms to alleviate disease progression. In addition to suppressing the production of inflammatory cytokines in the stomach and preventing the destruction of parietal cells, we show that iTregs secrete numerous chemokines and regulate both iTreg and effector T cell trafficking into the stomach. These data support efforts to use iTregs in therapies to treat autoimmunity and inflammatory diseases and provide novel insight into the biological mechanisms of iTreg-mediated immune suppression. The Journal of Immunology, 2011, 187: 1745-1753.