Laouar Yasmina, Sutterwala Fayyaz S, Gorelik Leonid, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nat Immunol. 2005 Jun;6(6):600-7. doi: 10.1038/ni1197. Epub 2005 Apr 24.
Interferon-gamma and interleukin 12 produced by the innate arm of the immune system are important regulators of T helper type 1 (T(H)1) cell development, but signals that negatively regulate their expression remain controversial. Here we show that transforming growth factor-beta (TGF-beta) controlled T(H)1 differentiation through the regulation of interferon-gamma produced by natural killer (NK) cells. Blockade of TGF-beta signaling in NK cells caused the accumulation of a large pool of NK cells secreting copious interferon-gamma, responsible for T(H)1 differentiation and protection from leishmania infection. In contrast, blockade of TGF-beta signaling in dendritic cells did not affect dendritic cell homeostasis or interleukin 12 production, thus indicating a previously undescribed demarcation of the function of TGF-beta in NK cells versus dendritic cells.
免疫系统先天性分支产生的干扰素-γ和白细胞介素12是1型辅助性T细胞（T(H)1）发育的重要调节因子，但负向调节其表达的信号仍存在争议。我们在此表明，转化生长因子-β（TGF-β）通过调节自然杀伤（NK）细胞产生的干扰素-γ来控制T(H)1分化。阻断NK细胞中的TGF-β信号会导致大量分泌大量干扰素-γ的NK细胞积累，这些NK细胞负责T(H)1分化并提供对利什曼原虫感染的保护。相比之下，阻断树突状细胞中的TGF-β信号并不影响树突状细胞的稳态或白细胞介素12的产生，从而表明TGF-β在NK细胞与树突状细胞中的功能存在此前未被描述的划分。
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