Department of Biological Sciences, Columbia University, New York, NY 10032, USA.
J Immunol. 2010 Mar 1;184(5):2638-45. doi: 10.4049/jimmunol.0902960. Epub 2010 Feb 1.
Dendritic cells (DCs) must achieve a critical balance between activation and tolerance, a process influenced by cytokines and growth factors. IL-10, which transduces signals through Stat3, has emerged as one important negative regulator of DC activation. To directly examine the role Stat3 plays in regulating DC activity, the Stat3 gene was targeted for deletion with a CD11c-cre transgene. Stat3 CKO mice developed cervical lymphadenopathy as well as a mild ileocolitis that persisted throughout life and was associated with impaired weight gain. Consistent with this, Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10-mediated suppression. These results reveal a cell-intrinsic negative regulatory role of Stat3 in DCs and link increased DC activation with perturbed immune homeostasis and chronic mucosal inflammation.
树突状细胞（DCs）必须在激活和耐受之间取得关键平衡，这一过程受细胞因子和生长因子的影响。白细胞介素-10（IL-10）通过 Stat3 转导信号，已成为 DC 激活的重要负调控因子之一。为了直接研究 Stat3 在调节 DC 活性中的作用，我们使用 CD11c-cre 转基因对 Stat3 基因进行了靶向敲除。Stat3 CKO 小鼠出现颈淋巴结病以及轻度回肠炎，这种疾病持续终生，并伴有体重增加受损。与此一致的是，Stat3 缺陷型 DC 表现出增强的免疫活性，包括增加细胞因子产生、Ag 依赖性 T 细胞激活以及对 IL-10 介导的抑制的抗性。这些结果揭示了 Stat3 在 DC 中具有细胞内负调节作用，并将 DC 激活与免疫稳态失调和慢性黏膜炎症联系起来。
